subject:(Immune tolerance)

University of Toronto

1. Nagy, Kristina. Acceptance of Allogeneic Cell Transplants without Systemic Immune Suppression.

Degree: PhD, 2020, University of Toronto

► Cell-based therapies hold great promise for the future of modern medicine. A large number of injuries and diseases that are currently not possible to cure… (more)

Subjects/Keywords: allograft tolerance; immune evasion; stem cells; tolerance; transplantation; 0379

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APA (6^th Edition):

Nagy, K. (2020). Acceptance of Allogeneic Cell Transplants without Systemic Immune Suppression. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/100950

Chicago Manual of Style (16^th Edition):

Nagy, Kristina. “Acceptance of Allogeneic Cell Transplants without Systemic Immune Suppression.” 2020. Doctoral Dissertation, University of Toronto. Accessed January 16, 2021. http://hdl.handle.net/1807/100950.

MLA Handbook (7^th Edition):

Nagy, Kristina. “Acceptance of Allogeneic Cell Transplants without Systemic Immune Suppression.” 2020. Web. 16 Jan 2021.

Vancouver:

Nagy K. Acceptance of Allogeneic Cell Transplants without Systemic Immune Suppression. [Internet] [Doctoral dissertation]. University of Toronto; 2020. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/1807/100950.

Council of Science Editors:

Nagy K. Acceptance of Allogeneic Cell Transplants without Systemic Immune Suppression. [Doctoral Dissertation]. University of Toronto; 2020. Available from: http://hdl.handle.net/1807/100950

East Carolina University

2. Thompson, Benjamin. Identification of Factors Associated with the Development and Decay of Heterologous Tolerance to Morphine in the Guinea Pig.

Degree: PhD, PHD-Pharmacology - Toxicology, 2016, East Carolina University

URL: http://hdl.handle.net/10342/5403

► It is believed that the heterologous tolerance that develops upon chronic exposure to morphine is the result of adaptive changes in the cellular signaling pathways… (more)

▼ It is believed that the heterologous tolerance that develops upon chronic exposure to morphine is the result of adaptive changes in the cellular signaling pathways associated with the [mu] opioid receptor. Proposed adaptive changes that occur in these signaling elements should occur as the changes in function appear in the whole animal and should spontaneously reverse as function returns to normal. The length of time it takes for these adaptations to reverse should be proportional to the magnitude of tolerance that has developed. To test these hypotheses, it is necessary to establish a complete time course for the development and decay of heterologous tolerance. Such a time course has been documented in the LM/MP of the guinea pig following pellet implantation. However, that method of administration only allows for a qualitative assessment of the nature of the decay of tolerance because the time at which morphine exposure ends is unknown. We therefore, assessed the capacity of two different twice daily injection administrations (subcutaneous and intraperitoneal) to generate a time course for the development and decay of heterologous tolerance that was reproducible. Animals were treated for 1, 2, 4, 7, or 10 days and then assessed for the appearance of tolerance via paw pressure testing in the whole animal and by measuring the response of the LM/MP to DAMGO and 2-CADO either 0, 1, 2, or 4 days after the last treatment day. Administration of morphine via intraperitoneal injection was found to produce tolerance that was highly variable, presumably due to variable absorption from the gut, making it unsuitable for the time course study. Subcutaneous injection was shown to reproducibly induce tolerance in both the whole animal via paw pressure analgesic testing and in the response of the guinea pig LM/MP to DAMGO and 2-CADO. The results of this study indicated that a significant level of tolerance begins to develop by 2 days of treatment which appears to become maximal and plateau by 4 days of treatment. In addition, the tolerance observed after 2 days is not heterologous as evidenced by the lack of a significant change in the IC50 value for 2-CADO in the LM/MP. By 4 days of treatment tolerance had become heterologous. Despite the plateau after 4 days of treatment, LM/MP responses from animals treated for 7 or 10 days of treatment took longer (4 days) to return to baseline than animals treated for 4 days (2 days). These data suggest that more extensive adaptations occur as treatment length increases despite the fact that the magnitude of change in the responses from the LM/MP and whole animal were not significantly different from each other after 4, 7, or 10 days of treatment. Western blot analysis of LM/MP and brainstem homogenates from these same animals revealed that heterologous tolerance in these tissues is not the result of a decrease in the receptor number of either the [mu], A1, A2a, or [alpha]2b receptors. A trend was observed for the [alpha]3 subunit isoform of the Na+/K+ ATPase in the LM/MP to… Advisors/Committee Members: Taylor, David A (advisor).

Subjects/Keywords: Pharmacology; Time Course; Drug Tolerance; Immune Tolerance; Guinea Pigs; Morphine

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Thompson, B. (2016). Identification of Factors Associated with the Development and Decay of Heterologous Tolerance to Morphine in the Guinea Pig. (Doctoral Dissertation). East Carolina University. Retrieved from http://hdl.handle.net/10342/5403

Chicago Manual of Style (16^th Edition):

Thompson, Benjamin. “Identification of Factors Associated with the Development and Decay of Heterologous Tolerance to Morphine in the Guinea Pig.” 2016. Doctoral Dissertation, East Carolina University. Accessed January 16, 2021. http://hdl.handle.net/10342/5403.

MLA Handbook (7^th Edition):

Thompson, Benjamin. “Identification of Factors Associated with the Development and Decay of Heterologous Tolerance to Morphine in the Guinea Pig.” 2016. Web. 16 Jan 2021.

Vancouver:

Thompson B. Identification of Factors Associated with the Development and Decay of Heterologous Tolerance to Morphine in the Guinea Pig. [Internet] [Doctoral dissertation]. East Carolina University; 2016. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/10342/5403.

Council of Science Editors:

Thompson B. Identification of Factors Associated with the Development and Decay of Heterologous Tolerance to Morphine in the Guinea Pig. [Doctoral Dissertation]. East Carolina University; 2016. Available from: http://hdl.handle.net/10342/5403

Carnegie Mellon University

3. Starzl, Ravi. Computational Modeling of Immune Signals.

Degree: 2012, Carnegie Mellon University

URL: http://repository.cmu.edu/dissertations/339

► The primary obstacle to enabling wide spread adoption of composite tissue transplantation, as well as to improving long term solid organ transplant outcomes, is establishing… (more)

▼ The primary obstacle to enabling wide spread adoption of composite tissue transplantation, as well as to improving long term solid organ transplant outcomes, is establishing a personalized medication regimen optimizing the balance between immunosuppression and immune function the individual minimum effective level of immunosuppression. Presently, the clinical gold standard for monitoring immune function is histologic inspection of biopsy for tissue damage, or monitoring blood chemistry for signs of organ failure. These trailing indicators reflect damage that has already accumulated, and are of little use in proactively determining the immunologic state of a patient. Samples collected from small animal surgical models were used to quantify the amount of immune signaling protein present (cytokines and chemokines) under various experimental conditions. Patterns in protein expression that reliably discriminate amongst the groups were then investigated with statistical inference methods such as the logistic classifier, decision tree, and random forest, operating in both the original feature space and in transformed feature spaces. This work demonstrates computational methods are effective in elucidating and classifying cytokine profiles, allowing the detection of rejection in composite tissue allografts well in advance of the current clinical gold standard, and shows that the methods can be effective in solid organ contexts as well. This work further determines that cytokine patterns of inflammation associated with rejection are specific to the structure and composition of the tissue in which they occur, and can be distinguished from immune signaling patterns associated with unspecific inflammation, wound healing, or immunosuppressed tissue. Clinical translation of these findings may provide novel computational tools that enable physicians to design personalized immunosuppression strategies for patients. The methods described in this work also provide information that can be used to investigate the biological basis for the observed immune signaling patterns. Further development may provide a computational framework for identifying novel therapeutic strategies in other pathologies.

Subjects/Keywords: computational immunology; immune signal modeling; transplant tolerance; toleragenic therapy; cytokine network; immune monitoring

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Starzl, R. (2012). Computational Modeling of Immune Signals. (Thesis). Carnegie Mellon University. Retrieved from http://repository.cmu.edu/dissertations/339

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Starzl, Ravi. “Computational Modeling of Immune Signals.” 2012. Thesis, Carnegie Mellon University. Accessed January 16, 2021. http://repository.cmu.edu/dissertations/339.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Starzl, Ravi. “Computational Modeling of Immune Signals.” 2012. Web. 16 Jan 2021.

Vancouver:

Starzl R. Computational Modeling of Immune Signals. [Internet] [Thesis]. Carnegie Mellon University; 2012. [cited 2021 Jan 16]. Available from: http://repository.cmu.edu/dissertations/339.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Starzl R. Computational Modeling of Immune Signals. [Thesis]. Carnegie Mellon University; 2012. Available from: http://repository.cmu.edu/dissertations/339

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Alberta

4. Wang, Szu-I. Proximal Impact of Transplant Tolerance-Promoting Antibody Therapies on Antigen-Specific T Cell Reactivity.

Degree: PhD, Department of Medical Microbiology and Immunology, 2013, University of Alberta

URL: https://era.library.ualberta.ca/files/1n79h5989

► The development of a transient, tolerance-promoting therapy is a critical goal in transplantation. Antibody-perturbation of T cell activation signals is considered a promising candidate. However,… (more)

▼ The development of a transient, tolerance-promoting therapy is a critical goal in transplantation. Antibody-perturbation of T cell activation signals is considered a promising candidate. However, the mechanisms of such therapies remain vague. The lack of cohesive and systematic knowledge in the requirements of generating long-term transplantation tolerance using short-term antibody treatments impedes the rational design of tolerance-promoting therapies. Therefore, using anti-LFA-1 and anti-CD154 as representatives of efficacious tolerance-inducing therapeutics, I interrogated their proximal impact on naïve antigen-specific T cells during initial antigen encounter. Using both monoclonal TCR-transgenic and polyclonal T cells in an in vivo adoptive transfer model, I tracked T cell activation and differentiation in the presence of anti-LFA-1 and/or anti-CD154. The antibody therapies markedly reduced the number of T cells in the draining lymph nodes. However, those remaining in the nodes vigorously proliferated. This paradoxical decrease in cell number despite intact proliferative capability was not due to deletion, as the adoptively transferred T cells persisted past primary activation and responded productively to secondary antigen exposure. Surprisingly, while anti-LFA-1 and/or anti-CD154 partially inhibited effector cytokine production, they did not specifically induce differentiation of alternate, tolerogenic phenotypes. However, while the antibody therapies mediated neither complete suppression of T cell reactivity nor T cell tolerance, anti-LFA-1- and anti-CD154-mediated skin graft prolongation was maintained by a dominant regulatory mechanism that allowed naïve graft-specific T cell activation and proliferation but inhibited their differentiation. Taken together, anti-LFA-1 and anti-CD154 appeared to partially inhibit T cell reactivity without inducing early T cell tolerance. However, long-term graft survival and tolerance generated by these antibodies were maintained by an active regulatory mechanism protecting the graft from naïve T cells. I therefore hypothesize that, instead of immediately generating tolerance upon interaction with responding T cells, antibodies targeting T cell activation signals dampen initial T cell reactivity to allow early transplant survival in an immunologically quiescent microenvironment, which allows the transplant itself to then gradually tolerize graft-specific T cells and generate donor-specific tolerance in a time-dependent manner. In other words, the transplant, and not the therapeutic antibodies, is the key tolerogen for successful generation of tolerance.

Subjects/Keywords: transplant survival; antibody therapy; immune tolerance; transplant; costimulation blockade; transplantation; T cells; transplantation tolerance; transplant tolerance

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wang, S. (2013). Proximal Impact of Transplant Tolerance-Promoting Antibody Therapies on Antigen-Specific T Cell Reactivity. (Doctoral Dissertation). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/1n79h5989

Chicago Manual of Style (16^th Edition):

Wang, Szu-I. “Proximal Impact of Transplant Tolerance-Promoting Antibody Therapies on Antigen-Specific T Cell Reactivity.” 2013. Doctoral Dissertation, University of Alberta. Accessed January 16, 2021. https://era.library.ualberta.ca/files/1n79h5989.

MLA Handbook (7^th Edition):

Wang, Szu-I. “Proximal Impact of Transplant Tolerance-Promoting Antibody Therapies on Antigen-Specific T Cell Reactivity.” 2013. Web. 16 Jan 2021.

Vancouver:

Wang S. Proximal Impact of Transplant Tolerance-Promoting Antibody Therapies on Antigen-Specific T Cell Reactivity. [Internet] [Doctoral dissertation]. University of Alberta; 2013. [cited 2021 Jan 16]. Available from: https://era.library.ualberta.ca/files/1n79h5989.

Council of Science Editors:

Wang S. Proximal Impact of Transplant Tolerance-Promoting Antibody Therapies on Antigen-Specific T Cell Reactivity. [Doctoral Dissertation]. University of Alberta; 2013. Available from: https://era.library.ualberta.ca/files/1n79h5989

University of Newcastle

5. Schjenken, John Even. Human endogenous retroviruses and immune tolerance in pregnancy.

Degree: PhD, 2011, University of Newcastle

URL: http://hdl.handle.net/1959.13/923742

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Research Doctorate - Doctor of Philosophy (PhD)

The human placenta expresses endogenous retroviral envelope proteins which have been postulated to play an important role in… (more)

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Research Doctorate - Doctor of Philosophy (PhD)

The human placenta expresses endogenous retroviral envelope proteins which have been postulated to play an important role in the physiology of pregnancy. Of these, syncytin-1 and syncytin-2 are highly expressed in the syncytiotrophoblast and cytotrophoblast respectively and are thought to be key factors in the regulation of syncytialisation due to their fusiogenic properties. In addition to their role in cell fusion, it has also been speculated that syncytin-1 and syncytin-2 may have a role in maternal immune tolerance due to the presence of the highly conserved immunosuppressive domain (ISD) within its sequence. However, no studies are yet to confirm this putative role. Another factor which has been speculated to have a role in maternal immune tolerance is Corticotropin Releasing Hormone (CRH) which has been shown to promote implantation and the maintenance of early pregnancy via the regulation of FasL. Interestingly, both syncytin-1 and FasL have been identified in immunosuppressive placental exosomes. Since CRH stimulates cyclic AMP (cAMP) production and syncytin-1, syncytin-2 and FasL are all stimulated by the cAMP second messenger pathway, it was hypothesised that syncytin-1 and syncytin-2 may be regulated by CRH. Further, it was hypothesised that syncytin-1 may contribute to the modulation of the maternal immune environment during pregnancy. To examine the regulation of syncytin-1 and syncytin-2 by CRH, a combined nucleic acid and protein extraction procedure was developed using column based nucleic acid extraction kits. Using 2D buffer, proteins extracted using this method were shown to have a comparable protein profile to conventionally extracted proteins. This method was then used to examine RNA and protein levels in CRH treated BeWo cells. Following CRH treatment of BeWo cells, a significant upregulation of syncytin-1, syncytin-2 and FasL mRNA was observed. CRH also increased the production of the syncytin-1 precursor in an exosomal fraction. To examine the immunosuppressive properties of syncytin-1, the recombinant ectodomains of human and mouse syncytins were produced and purified using a combination of affinity chromatography and gel filtration. The immunosuppressive properties of the syncytin-1 recombinant ectodomain were then tested using a whole blood culture model stimulated with LPS or PHA. Syncytin-1 recombinant ectodomain at a concentration of 1µM inhibited the production of TNF-α by 50% and CXCL10 by 65% in whole blood cultures following maximal stimulation with LPS. Syncytin-1 recombinant ectodomain also inhibited the production of IFN-γ by 30% in PHA stimulated PBMC. These studies demonstrate for the first time that syncytin-1 has immunosuppressive properties. Further, these studies show that CRH has a role in the stimulation of syncytin-1 and its subsequent sorting into exosomes. Circulating placental exosomes containing syncytin-1 and other immunosuppressive factors including FasL may interact with maternal immune cells to prevent an immune…

Advisors/Committee Members: University of Newcastle. Faculty of Health, School of Medicine and Public Health.

Subjects/Keywords: endogenous retroviruses; pregnancy; syncytialisation regulation; immune tolerance; immunosuppression

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Schjenken, J. E. (2011). Human endogenous retroviruses and immune tolerance in pregnancy. (Doctoral Dissertation). University of Newcastle. Retrieved from http://hdl.handle.net/1959.13/923742

Chicago Manual of Style (16^th Edition):

Schjenken, John Even. “Human endogenous retroviruses and immune tolerance in pregnancy.” 2011. Doctoral Dissertation, University of Newcastle. Accessed January 16, 2021. http://hdl.handle.net/1959.13/923742.

MLA Handbook (7^th Edition):

Schjenken, John Even. “Human endogenous retroviruses and immune tolerance in pregnancy.” 2011. Web. 16 Jan 2021.

Vancouver:

Schjenken JE. Human endogenous retroviruses and immune tolerance in pregnancy. [Internet] [Doctoral dissertation]. University of Newcastle; 2011. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/1959.13/923742.

Council of Science Editors:

Schjenken JE. Human endogenous retroviruses and immune tolerance in pregnancy. [Doctoral Dissertation]. University of Newcastle; 2011. Available from: http://hdl.handle.net/1959.13/923742

University of Miami

6. Lui, Jen Bon. Gut-associated Cross-differentiation of T Lymphocyte Lineages.

Degree: PhD, Microbiology and Immunology (Medicine), 2016, University of Miami

URL: https://scholarlyrepository.miami.edu/oa_dissertations/1775

► The gut microbiota is an important symbiotic contributor to human health. They provide essential nutrients and prevent colonization by pathogenic bacteria. Furthermore, the gut microbiota… (more)

Subjects/Keywords: immune tolerance; lineage plasticity; T cells; Treg; lamina propria; microbiota

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lui, J. B. (2016). Gut-associated Cross-differentiation of T Lymphocyte Lineages. (Doctoral Dissertation). University of Miami. Retrieved from https://scholarlyrepository.miami.edu/oa_dissertations/1775

Chicago Manual of Style (16^th Edition):

Lui, Jen Bon. “Gut-associated Cross-differentiation of T Lymphocyte Lineages.” 2016. Doctoral Dissertation, University of Miami. Accessed January 16, 2021. https://scholarlyrepository.miami.edu/oa_dissertations/1775.

MLA Handbook (7^th Edition):

Lui, Jen Bon. “Gut-associated Cross-differentiation of T Lymphocyte Lineages.” 2016. Web. 16 Jan 2021.

Vancouver:

Lui JB. Gut-associated Cross-differentiation of T Lymphocyte Lineages. [Internet] [Doctoral dissertation]. University of Miami; 2016. [cited 2021 Jan 16]. Available from: https://scholarlyrepository.miami.edu/oa_dissertations/1775.

Council of Science Editors:

Lui JB. Gut-associated Cross-differentiation of T Lymphocyte Lineages. [Doctoral Dissertation]. University of Miami; 2016. Available from: https://scholarlyrepository.miami.edu/oa_dissertations/1775

University of Manchester

7. Miller, Jonathan. Modulation of dendritic cells and autoimmunity by apoptotic and necrotic cells.

Degree: PhD, 2011, University of Manchester

URL: https://www.research.manchester.ac.uk/portal/en/theses/modulation-of-dendritic-cells-and-autoimmunity-by-apoptotic-and-necrotic-cells(eab00223-e5a2-4fdd-8baf-aa5966c87ede).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.538416

► As the principal antigen-presenting cells to T cells, dendritic cells (DCs) have a key role in the balance of immunity and autoimmunity. They are essential… (more)

▼ As the principal antigen-presenting cells to T cells, dendritic cells (DCs) have a key role in the balance of immunity and autoimmunity. They are essential in two major, converse roles - eliciting T cell immune responses to pathogenic material, and maintaining peripheral tolerance to self-tissue by inhibiting self-reactive T cells. These functions involve the processing of pathogenic or self antigens and subsequent presentation of antigenic peptides on MHC to antigen-specific T cells. DC recognition of conserved pathogenic markers induces a mature phenotype that governs immunogenic presentation to T cells and, consequently, the adaptive immune response. In contrast, DC recognition of self tissue suppresses maturation, instead inducing a tolerogenic phenotype that induces self antigen-specific T cell to die, become anergised, or converted to T regulatory cells. Apoptotic cells are the major source of self-antigen for the maintenance of peripheral tolerance, and their defective clearance by DCs is implicated in autoimmunity. Apoptotic cells are thought to actively suppress maturation of DCs and inhibit the possible immune responses promoted by proinflammatory mediators released from necrotic cells. However, the immune function of apoptotic cells and their relative influence over necrotic cells are highly contested, partially due to the complex nature of immunogenicity arising from the sourcing and generation of apoptotic cells. In this investigation, various methods of inducing apoptosis and necrosis are evaluated. Definitive methods of inducing well-characterised cell death are then employed to compare the effects of apoptotic and necrotic cells on dendritic cells and in vitro and in vivo immune responses. Reported here are in vitro findings that support previous reports of the anti-inflammatory response of DCs to apoptotic cells, and the inflammatory response of DCs to necrotic cells. The previously-reported inhibitory effect of apoptotic cells on LPS-induced secretion of Th1 cytokines is supported here, but the inhibitory effect of apoptotic cells on LPS-induced upregulation of co-stimulatory molecules is contested. Novel findings describe the upregulation of DC expression of co-inhibitory molecules induced by both apoptotic cells and necrotic cells. Apoptotic cells, but not necrotic cells, had a suppressive effect on CpG-induced upregulation of co-stimulatory molecules and pro-inflammatory cytokines. Apoptotic cells suppressed the capacity of untreated and CpG-treated, but not LPS-treated, DCs to elicit IFNγ production by T cells. Apoptotic cells, but not necrotic cells, induced regulatory T cells and partially restored their CpG-suppressed induction. Finally, apoptotic cell-modulation of DCs inhibited the induction of autoimmunity in a novel modification of an in vivo model of diabetes. Interestingly, novel evidence for the possibility of necrotic cell-induced tolerance by means of direct T cell killing is addressed.

Subjects/Keywords: 571.96; Dendritic cell; Autoimmunity; Immune tolerance; Apoptotic cell; Necrotic cell

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Miller, J. (2011). Modulation of dendritic cells and autoimmunity by apoptotic and necrotic cells. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/modulation-of-dendritic-cells-and-autoimmunity-by-apoptotic-and-necrotic-cells(eab00223-e5a2-4fdd-8baf-aa5966c87ede).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.538416

Chicago Manual of Style (16^th Edition):

Miller, Jonathan. “Modulation of dendritic cells and autoimmunity by apoptotic and necrotic cells.” 2011. Doctoral Dissertation, University of Manchester. Accessed January 16, 2021. https://www.research.manchester.ac.uk/portal/en/theses/modulation-of-dendritic-cells-and-autoimmunity-by-apoptotic-and-necrotic-cells(eab00223-e5a2-4fdd-8baf-aa5966c87ede).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.538416.

MLA Handbook (7^th Edition):

Miller, Jonathan. “Modulation of dendritic cells and autoimmunity by apoptotic and necrotic cells.” 2011. Web. 16 Jan 2021.

Vancouver:

Miller J. Modulation of dendritic cells and autoimmunity by apoptotic and necrotic cells. [Internet] [Doctoral dissertation]. University of Manchester; 2011. [cited 2021 Jan 16]. Available from: https://www.research.manchester.ac.uk/portal/en/theses/modulation-of-dendritic-cells-and-autoimmunity-by-apoptotic-and-necrotic-cells(eab00223-e5a2-4fdd-8baf-aa5966c87ede).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.538416.

Council of Science Editors:

Miller J. Modulation of dendritic cells and autoimmunity by apoptotic and necrotic cells. [Doctoral Dissertation]. University of Manchester; 2011. Available from: https://www.research.manchester.ac.uk/portal/en/theses/modulation-of-dendritic-cells-and-autoimmunity-by-apoptotic-and-necrotic-cells(eab00223-e5a2-4fdd-8baf-aa5966c87ede).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.538416

University of Sydney

8. Hsu, Peter Shang-Yu. The role of interleukin 10 in immune tolerance – lessons learnt from human pregnancy .

Degree: 2014, University of Sydney

URL: http://hdl.handle.net/2123/12131

► Pregnancy requires that the maternal immune system tolerates the semi-allogeneic fetus and therefore represents an important model for the study of human immune tolerance. The… (more)

Subjects/Keywords: Immune tolerance; human pregnancy; Interleukin 10; regulatory T cells

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hsu, P. S. (2014). The role of interleukin 10 in immune tolerance – lessons learnt from human pregnancy . (Thesis). University of Sydney. Retrieved from http://hdl.handle.net/2123/12131

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Hsu, Peter Shang-Yu. “The role of interleukin 10 in immune tolerance – lessons learnt from human pregnancy .” 2014. Thesis, University of Sydney. Accessed January 16, 2021. http://hdl.handle.net/2123/12131.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Hsu, Peter Shang-Yu. “The role of interleukin 10 in immune tolerance – lessons learnt from human pregnancy .” 2014. Web. 16 Jan 2021.

Vancouver:

Hsu PS. The role of interleukin 10 in immune tolerance – lessons learnt from human pregnancy . [Internet] [Thesis]. University of Sydney; 2014. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/2123/12131.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hsu PS. The role of interleukin 10 in immune tolerance – lessons learnt from human pregnancy . [Thesis]. University of Sydney; 2014. Available from: http://hdl.handle.net/2123/12131

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

9. Bartolo, Laurent. Réponses immunitaires et induction de tolérance pour la thérapie génique rAAV du muscle basée sur le ciblage des hépatocytes : induction de tolérance et mécanismes immunitaires liés à la transduction des hépatocytes : Immune responses and liver-based avoidance strategy in rAVV muscle gene therapy.

Degree: Docteur es, Immunologie, 2018, Sorbonne Paris Cité

URL: http://www.theses.fr/2018USPCB198

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Les réponses immunes contre les traitements de thérapie génique rAAV, dirigées non seulement contre la capside du vecteur, mais aussi contre le transgène, représentent un… (more)

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Les réponses immunes contre les traitements de thérapie génique rAAV, dirigées non seulement contre la capside du vecteur, mais aussi contre le transgène, représentent un défi majeur en particulier dans le contexte d'un transfert de gènes vers le muscle pour le traitement de diverses maladies monogéniques du muscle. Cette thèse est focalisée sur la réponse dirigée contre le transgène. Celle-ci se met en place contre des éléments du transgène thérapeutique qui ne sont pas initialement présents, ou insuffisamment exprimés, chez l'hôte et peut entraîner l'élimination des cellules qui produisent le transgène. Dans ce contexte il est nécessaire de concevoir des protocoles de traitement capable d'imposer en périphérie une tolérance immunitaire spécifique du transgène. Nous avons exploré comment l'induction de l'expression d'un transgène étranger dans le foie à l'aide d'un vecteur rAAV impose une tolérance immunologique après transduction du muscle, et ceci malgré l'initiation dans le muscle d'une réponse T CD8+ et CD4+ dirigé contre le transgène. Nous avons démontré que l'expression du transgène dans le foie promeut une tolérance immunitaire envers une injection du vecteur rAAV dans le muscle et ce malgré la présence d'une réponse mémoire spécifique du transgène. Sur le plan de la réponse T CD8+, nous constatons une délétion totale ou partielle ainsi qu'une conversion des cellules vers un phénotype d'épuisement, avec l'expression du marqueur PD-1. La présence d'une réponse T CD4+ mémoire contre le transgène, ne semble pas altérer la tolérance induite par le foie. Nous discutons ensuite, en nous confrontant aux auteurs du domaine, le mécanisme global éventuellement mis en jeu : Une fois la réponse adaptative complète T CD8+ et T CD4+ initiée dans le ganglion drainant le muscle, ces cellules T doivent, avant de retourner vers le muscle, circuler par le foie. Dans le foie, elles s'y accumulent et rencontrent une seconde fois l'antigène, ce qui semble conduire à l'épuisement, suite à l'expression de PD-1, ou à la mort des cellules T CD8+ par un mécanisme décrit sous le nom d'emperipolesis suicidaire ou d'apoptose dépendant du facteur BIM. Les cellules CD4+, elle, ne subiraient pas de délétion, mais une éventuelle modification phénotypique, vers un phénotype tolérogène ou suppresseur. Ce processus serait dépendant de la rétention des cellules T dans le foie que nous avons mis en évidence, ainsi que de l'affinité de la réponse contre le transgène qui rend compte de nos résultats. Nous exposons finalement le domaine d'application de notre méthode, permettant de surmonter une réponse locale initiée dans le muscle, ce qui peut s'avérer crucial pour le traitement par thérapie génique des dystrophies musculaires monogéniques, basé sur l'emploi de transgènes potentiellement immunogènes dû au défaut d'expression chez le receveur.

It is increasingly realized that immune responses to rAAV gene therapy treatments, not only to the vector capsid but also to reparative transgenes can cause adverse effects of importance in the case of…

Advisors/Committee Members: Davoust, Jean (thesis director).

Subjects/Keywords: Thérapie génique; Réponse immunitaire; Tolérance immunitaire; Foie; Muscle; Lymphocyte T; Gene therapy; Immune response; Immune tolerance; Liver; Muscle; T lymphocyte; 615.895

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bartolo, L. (2018). Réponses immunitaires et induction de tolérance pour la thérapie génique rAAV du muscle basée sur le ciblage des hépatocytes : induction de tolérance et mécanismes immunitaires liés à la transduction des hépatocytes : Immune responses and liver-based avoidance strategy in rAVV muscle gene therapy. (Doctoral Dissertation). Sorbonne Paris Cité. Retrieved from http://www.theses.fr/2018USPCB198

Chicago Manual of Style (16^th Edition):

Bartolo, Laurent. “Réponses immunitaires et induction de tolérance pour la thérapie génique rAAV du muscle basée sur le ciblage des hépatocytes : induction de tolérance et mécanismes immunitaires liés à la transduction des hépatocytes : Immune responses and liver-based avoidance strategy in rAVV muscle gene therapy.” 2018. Doctoral Dissertation, Sorbonne Paris Cité. Accessed January 16, 2021. http://www.theses.fr/2018USPCB198.

MLA Handbook (7^th Edition):

Bartolo, Laurent. “Réponses immunitaires et induction de tolérance pour la thérapie génique rAAV du muscle basée sur le ciblage des hépatocytes : induction de tolérance et mécanismes immunitaires liés à la transduction des hépatocytes : Immune responses and liver-based avoidance strategy in rAVV muscle gene therapy.” 2018. Web. 16 Jan 2021.

Vancouver:

Bartolo L. Réponses immunitaires et induction de tolérance pour la thérapie génique rAAV du muscle basée sur le ciblage des hépatocytes : induction de tolérance et mécanismes immunitaires liés à la transduction des hépatocytes : Immune responses and liver-based avoidance strategy in rAVV muscle gene therapy. [Internet] [Doctoral dissertation]. Sorbonne Paris Cité; 2018. [cited 2021 Jan 16]. Available from: http://www.theses.fr/2018USPCB198.

Council of Science Editors:

Bartolo L. Réponses immunitaires et induction de tolérance pour la thérapie génique rAAV du muscle basée sur le ciblage des hépatocytes : induction de tolérance et mécanismes immunitaires liés à la transduction des hépatocytes : Immune responses and liver-based avoidance strategy in rAVV muscle gene therapy. [Doctoral Dissertation]. Sorbonne Paris Cité; 2018. Available from: http://www.theses.fr/2018USPCB198

10. Gorvel, Laurent. Cellules dendritiques : infection et immunité tissulaire : Dendritic cells : response to infection and tissue immunity.

Degree: Docteur es, Pathologie humaine. Maladies infectieuses, 2013, Aix Marseille Université

URL: http://www.theses.fr/2013AIXM5089

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Les cellules dendritiques (DCs) jouent un rôle essentiel dans la réponse immunitaire. En effet leur fonction de présentation de l’antigène les place au cœur de… (more)

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Les cellules dendritiques (DCs) jouent un rôle essentiel dans la réponse immunitaire. En effet leur fonction de présentation de l’antigène les place au cœur de l’induction de la réponse immunitaire adaptative. Ceci, les rends vulnérables aux attaques des agents pathogènes. En effet de nombreux agents pathogènes détournent la réponse des DCs. Je me suis donc proposé d’étudier la réponse des DCs à Tropheryma whipplei, Coxiella burnetii, Brucella abortus et Orientia tsutsugamushi. J’ai pu mettre en évidence un défaut de maturation des DCs infectées par C. burnetii et B. abortus, liée à un défaut de la voie de l’interféron (IFN) de type I et de secretion de l'IFN-b. La deuxième partie de ma thèse replace le système immunitaire inné dans le cadre de l’immunité tissulaire humaine. Je me suis premièrement intéressé aux macrophages placentaires. J’ai pu démontrer que la capacité des macrophages placentaires à former des MGCs est altérée lors d’une chorioamniotite, ce qui laisse supposer que ces cellules géantes jouent un rôle dans le maintient de la tolérance fœto-maternelle. Deuxièmement je me suis intéressé aux DCs placentaires (plaDCs). J’ai ainsi put démontrer que les plaDCs sont de véritables DCs myéloïdes conditionnées par leur environnement direct ou hormonal au cours de la grossesse. Mon travail illustre deux concepts, le premier démontre la nécessité d’utiliser des techniques à haut débit pour identifier les perturbations induites par plusieurs agents pathogènes. Le deuxième démontre que l’environnement des cellules immunitaires participe fortement à leurs réponses face à des agents pathogènes mais également sur leur phénotype et fonction.

Dendritic cells (DCs) play a key role in the immune response. Indeed, their antigen presenting function allows them to be considered as the main inducers of adaptive response. This pivotal role also makes vulnerable to pathogen attacks. Indeed, numerous pathogens target DC response to avoid a microbicidal adaptive immunity to take place. To understand these mecanisms, I investigated the response of DCs to T. whipplei, C. burnetii, B. abortus and O. tsutsugamushi. I could highlight a phenotypic but not functional defect of maturation in DCs infected by C. burnetii and B. abortus, which was related to a defect in type I IFN response. Indeed, C. burnetii and B. abortus did not induce the production of IFN-b and induced an abnormal phosphorylation of MAPKs, known to participate to DC maturation. In this study, I could demonstrate that C. burnetii and B. abortus interfere with type I IFN response. The second part of my thesis dealt with innate immune system in the human tissue. First I interested myself in placental macrophages. I demonstrated that placental macrophages ability to form MGCs was altered in chorioamnionitis, suggesting that MGCs play a role in tolerance as they disappear in an infectious pathology. Second, I interested myself in placental DCs (plaDCs) for which I could conclude that plaDCs are true myeloid DCs that are polarized by their microenvironment. My work…

Advisors/Committee Members: Mège, Jean-Louis (thesis director).

Subjects/Keywords: Cellules dendritiques; Placenta; Macrophage; Maturation; Réponse immune; Tolérence; Dendritic cells; Placenta,; Macrophages; Maturation; Immune response; Tolerance

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Gorvel, L. (2013). Cellules dendritiques : infection et immunité tissulaire : Dendritic cells : response to infection and tissue immunity. (Doctoral Dissertation). Aix Marseille Université. Retrieved from http://www.theses.fr/2013AIXM5089

Chicago Manual of Style (16^th Edition):

Gorvel, Laurent. “Cellules dendritiques : infection et immunité tissulaire : Dendritic cells : response to infection and tissue immunity.” 2013. Doctoral Dissertation, Aix Marseille Université. Accessed January 16, 2021. http://www.theses.fr/2013AIXM5089.

MLA Handbook (7^th Edition):

Gorvel, Laurent. “Cellules dendritiques : infection et immunité tissulaire : Dendritic cells : response to infection and tissue immunity.” 2013. Web. 16 Jan 2021.

Vancouver:

Gorvel L. Cellules dendritiques : infection et immunité tissulaire : Dendritic cells : response to infection and tissue immunity. [Internet] [Doctoral dissertation]. Aix Marseille Université 2013. [cited 2021 Jan 16]. Available from: http://www.theses.fr/2013AIXM5089.

Council of Science Editors:

Gorvel L. Cellules dendritiques : infection et immunité tissulaire : Dendritic cells : response to infection and tissue immunity. [Doctoral Dissertation]. Aix Marseille Université 2013. Available from: http://www.theses.fr/2013AIXM5089

11. Charaix, Jonathan. La cytokine lymphotoxine α et le facteur de transcription Aire régulent la signature suppressive des lymphocytes T régulateurs : The cytokine Lymphotoxin a and the transcription factor Aire regulate the suppressive signature of regulatory T cells.

Degree: Docteur es, Immunologie, 2019, Aix Marseille Université

URL: http://www.theses.fr/2019AIXM0507

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Les lymphocytes T régulateurs (Treg) de phénotype Foxp3+ inhibent en périphérie les réactions immunitaires autoréactives, prévenant ainsi l’apparition de pathologies inflammatoires et auto-immunes. Des essais… (more)

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Les lymphocytes T régulateurs (Treg) de phénotype Foxp3+ inhibent en périphérie les réactions immunitaires autoréactives, prévenant ainsi l’apparition de pathologies inflammatoires et auto-immunes. Des essais cliniques prometteurs basés sur l’injection de Treg restent actuellement limités par la quantité de cellules requise et nécessitent donc l’identification de molécules aptes à promouvoir l’activité suppressive des Treg afin de faciliter leur utilisation en thérapie.Des résultats préliminaires de mon équipe indiquent que les Treg expriment fortement la cytokine lymphotoxine α (LTa), suggérant un rôle crucial de cette molécule dans la biologie du Treg. Mes travaux démontrent que les Treg Lta-déficients présentent une activité fortement suppressive et atténue efficacement le développement de diverses pathologies inflammatoires et auto-immunes. Ainsi, la LTα constitue une nouvelle cible thérapeutique permettant d’augmenter l’activité suppressive des Treg. Le facteur de transcription Aire contrôle partiellement la recirculation thymique des Treg périphériques. Cependant, le rôle d’Aire dans la biologie de ces cellules reste inconnu. Mes résultats indiquent qu’Aire régule la prolifération et la signature suppressive des Treg recirculants au cours de la vie. En conséquence, les Treg recirculants dans le thymus de souris Aire-déficientes présentent une activité suppressive altérée et sont incapables d’atténuer le développement d’une auto-immunité multi-organes.Les résultats obtenus au cours de mon doctorat visent identifier de nouvelles stratégies thérapeutiques basées sur les Treg afin de soigner, à terme, différentes pathologies inflammatoires et auto-immunes.

Regulatory T lymphocytes (Treg) with a Foxp3+ phenotype inhibits in the periphery autoreactive immune responses, thus preventing the emergence of inflammatory and autoimmune diseases. Promising clinical trials based on Treg injection currently remain limited by the required quantity of cells and thus, necessitate the identification of molecules that promote Treg suppressive activity in order facilitate their use in therapy. Preliminary results from my research team indicate that Treg highly express the cytokine lymphotoxin α (LTa), suggesting a crucial role of this molecule in Treg biology. My results demonstrate that Treg from Lta-deficient mice exhibit a highly suppressive activity and attenuates efficiently the development of various inflammatory and autoimmune pathologies. Therefore, LTα represents a new therapeutic target to increase Treg suppressive activity. The transcription factor Aire partially controls the thymic recirculation of peripheral Treg. However, the role of Aire in the biology of these cells remains unknown. My results indicate that Aire regulates the proliferation and the suppressive signature of recirculating Treg throughout life. Therefore, recirculating Treg in the thymus of Aire-deficient mice show a diminished suppressive activity and are unable to attenuate the emergence of a multi-organ autoimmunity.Results obtained during my PhD…

Advisors/Committee Members: Irla, Magali (thesis director).

Subjects/Keywords: Treg; Thymus; LTa; Aire; Tolérance immunitaire; Treg; Thymus; LTa; Aire; Immune tolerance; 571

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Charaix, J. (2019). La cytokine lymphotoxine α et le facteur de transcription Aire régulent la signature suppressive des lymphocytes T régulateurs : The cytokine Lymphotoxin a and the transcription factor Aire regulate the suppressive signature of regulatory T cells. (Doctoral Dissertation). Aix Marseille Université. Retrieved from http://www.theses.fr/2019AIXM0507

Chicago Manual of Style (16^th Edition):

Charaix, Jonathan. “La cytokine lymphotoxine α et le facteur de transcription Aire régulent la signature suppressive des lymphocytes T régulateurs : The cytokine Lymphotoxin a and the transcription factor Aire regulate the suppressive signature of regulatory T cells.” 2019. Doctoral Dissertation, Aix Marseille Université. Accessed January 16, 2021. http://www.theses.fr/2019AIXM0507.

MLA Handbook (7^th Edition):

Charaix, Jonathan. “La cytokine lymphotoxine α et le facteur de transcription Aire régulent la signature suppressive des lymphocytes T régulateurs : The cytokine Lymphotoxin a and the transcription factor Aire regulate the suppressive signature of regulatory T cells.” 2019. Web. 16 Jan 2021.

Vancouver:

Charaix J. La cytokine lymphotoxine α et le facteur de transcription Aire régulent la signature suppressive des lymphocytes T régulateurs : The cytokine Lymphotoxin a and the transcription factor Aire regulate the suppressive signature of regulatory T cells. [Internet] [Doctoral dissertation]. Aix Marseille Université 2019. [cited 2021 Jan 16]. Available from: http://www.theses.fr/2019AIXM0507.

Council of Science Editors:

Charaix J. La cytokine lymphotoxine α et le facteur de transcription Aire régulent la signature suppressive des lymphocytes T régulateurs : The cytokine Lymphotoxin a and the transcription factor Aire regulate the suppressive signature of regulatory T cells. [Doctoral Dissertation]. Aix Marseille Université 2019. Available from: http://www.theses.fr/2019AIXM0507

University of Gothenburg / Göteborgs Universitet

12. Mjörnstedt, Lars, 1956-. Mechanisms in experimental transplantation tolerance.

Degree: 1986, University of Gothenburg / Göteborgs Universitet

URL: http://hdl.handle.net/2077/13064

Subjects/Keywords: Kirurgi Transplantation Heart: transplantation; Immune tolerance

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mjörnstedt, Lars, 1. (1986). Mechanisms in experimental transplantation tolerance. (Thesis). University of Gothenburg / Göteborgs Universitet. Retrieved from http://hdl.handle.net/2077/13064

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Mjörnstedt, Lars, 1956-. “Mechanisms in experimental transplantation tolerance.” 1986. Thesis, University of Gothenburg / Göteborgs Universitet. Accessed January 16, 2021. http://hdl.handle.net/2077/13064.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Mjörnstedt, Lars, 1956-. “Mechanisms in experimental transplantation tolerance.” 1986. Web. 16 Jan 2021.

Vancouver:

Mjörnstedt, Lars 1. Mechanisms in experimental transplantation tolerance. [Internet] [Thesis]. University of Gothenburg / Göteborgs Universitet; 1986. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/2077/13064.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Mjörnstedt, Lars 1. Mechanisms in experimental transplantation tolerance. [Thesis]. University of Gothenburg / Göteborgs Universitet; 1986. Available from: http://hdl.handle.net/2077/13064

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Melbourne

13. Chee, Hui En Jonathan. The development and regulation of islet-specific T cells in an experimental model of autoimmune diabetes.

Degree: 2014, University of Melbourne

URL: http://hdl.handle.net/11343/42157

► Type 1 diabetes (T1D) is an autoimmune disease. T cells specific for β-cell antigens such as proinsulin and islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP)… (more)

▼ Type 1 diabetes (T1D) is an autoimmune disease. T cells specific for β-cell antigens such as proinsulin and islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP) are important in mediating the disease. The aims of this thesis were to study the development and regulation of T cells in the development of autoimmune diabetes in the non-obese diabetic (NOD) mouse model. Chapter 2 describes the development of IGRP-specific CD8+ T cells in autoimmune diabetes. IGRP-specific T cells in the mouse were tracked using a sensitive MHC-tetramer based magnetic enrichment. There was an increase in the number of IGRP-specific T cells in the peripheral blood and lymphoid tissue as mice age, and the increase correlated with insulitis progression. These cells had an effector-memory phenotype, which was only acquired in the inflammatory environment of the islets, and not the draining lymph nodes. Islet-specific T cells could also migrate from islets into the periphery. In the development of autoimmune diabetes, important changes to IGRP-specific T cells during the pathogenesis of diabetes occur not in the draining lymph nodes but in the islets, where they expand and differentiate into effector-memory T cells, and emigrate to the periphery, where they can report progression of islet pathology. Tumour Necrosis Factor (TNF) is an inflammatory cytokine that has been implicated in the pathogenesis of autoimmune diabetes. In chapter 3, we investigate the effects of TNF-TNFR1 signalling deficiency on the development of autoimmune diabetes, by using a NOD mouse deficient in TNF receptor 1 (TNFR1). TNFR1-/- islets grafted onto kidney capsule of diabetic mice were destroyed, showing that TNFR1 deficiency on β-cell did not confer protection against immune destruction. The specific effects of TNFR1 deficiency on the immune system of NOD mice were also examined. Adoptively transferred β-cell specific T cells proliferated normally in the pancreatic lymph nodes, but failed to migrate into the pancreas of TNFR1-/- recipient mice. Notably, analysis of immune cell subsets by flow cytometry showed an increased percentage of CD4+CD25+Foxp3+ T regulatory cells in TNFR1 deficient mice. Depletion of CD4+CD25+ regulatory T cells using GK1.5 CD4 depleting mAb restored diabetes in NOD8.3/TNFR1-/- mice. These results suggest that blockade of TNF signalling suppresses diabetes by increasing regulatory functions of the immune system. T cell responses to insulin (INS) are crucial in development of T1D. Chapter 4 of the thesis examines insulin-specific T cells in NOD mice, and in NOD mice tolerant to proinsulin II (NODPI), which do not develop diabetes or insulitis. There was no significant difference in the absolute number of insulin-specific CD8+ T-cells in NOD and NODPI mice. INS-specific CD8+ T-cells in NOD mice expanded significantly more in response to stimulation by peptide compared to NODPI. In vivo cytotoxic activity in NODPI was reduced compared to NOD. The absolute number of INS-specific CD4+ T-cells in NOD and NODPI…

Subjects/Keywords: type 1 diabetes; T cells; autoimmunity; immunology; immune tolerance; cyotkines; TNF; IGRP; proinsulin

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Chee, H. E. J. (2014). The development and regulation of islet-specific T cells in an experimental model of autoimmune diabetes. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/42157

Chicago Manual of Style (16^th Edition):

Chee, Hui En Jonathan. “The development and regulation of islet-specific T cells in an experimental model of autoimmune diabetes.” 2014. Doctoral Dissertation, University of Melbourne. Accessed January 16, 2021. http://hdl.handle.net/11343/42157.

MLA Handbook (7^th Edition):

Chee, Hui En Jonathan. “The development and regulation of islet-specific T cells in an experimental model of autoimmune diabetes.” 2014. Web. 16 Jan 2021.

Vancouver:

Chee HEJ. The development and regulation of islet-specific T cells in an experimental model of autoimmune diabetes. [Internet] [Doctoral dissertation]. University of Melbourne; 2014. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/11343/42157.

Council of Science Editors:

Chee HEJ. The development and regulation of islet-specific T cells in an experimental model of autoimmune diabetes. [Doctoral Dissertation]. University of Melbourne; 2014. Available from: http://hdl.handle.net/11343/42157

University of Maryland

14. Tostanoski, Lisa Hoban. Engineering biomaterials to promote systemic, antigen-specific tolerance.

Degree: Bioengineering, 2017, University of Maryland

URL: http://hdl.handle.net/1903/20276

► In autoimmune diseases, such as multiple sclerosis (MS) and type 1 diabetes, the immune system incorrectly identifies and attacks “self” molecules. Existing therapies have provided… (more)

▼ In autoimmune diseases, such as multiple sclerosis (MS) and type 1 diabetes, the immune system incorrectly identifies and attacks “self” molecules. Existing therapies have provided important benefits, but are limited by off-target effects, reduced efficacy as disease progresses, and lack of cure potential, necessitating frequent, life-long dosing. An exciting strategy being explored is the design of vaccine-like therapies that selectively reprogram immune responses to self-molecules. This approach could, for example, control the attack of myelin – the protective coating around neurons – that occurs during MS, without leaving patients immunocompromised. However, the realization of this idea has proven difficult; once injected, conventional approaches do not provide control over the combinations, concentrations, and kinetics of signals that reach key tissues that orchestrate immune responses, such as lymph nodes (LNs). Biomaterials have emerged as a promising strategy to confront this challenge, offering features including co-delivery of cargos and controlled release kinetics. The research in this dissertation harnesses biomaterials to develop novel strategies to promote effective, yet selective control of autoimmunity, termed antigen-specific tolerance. In the first aim, direct injection was used to deposit degradable microparticles in LNs, enabling local controlled release of combinations of myelin peptide and Rapamycin, a drug shown to promote regulatory immune function. This work demonstrates the potency of intra-LN delivery in mouse models of MS, as a single dose of co-loaded microparticles permanently reversed disease-induced paralysis in a myelin-specific manner. The results also support this approach as a platform to study the link between local LN signaling and resultant responses in non-treated tissues and sites of disease during autoimmunity. In the second aim, myelin peptide and GpG, a regulatory ligand of an inflammatory pathway overactive in mouse models and patients with autoimmunity, were self-assembled. This approach generated microcapsules that mimic attractive features of conventional biomaterials, but eliminate synthetic carrier components that can complicate rational design and, due to intrinsic inflammatory properties, might exacerbate autoimmunity. These materials promoted tolerance in mouse cells, mouse models of MS, and samples from human MS patients. Together, these strategies could offer novel, modular approaches to combat autoimmune diseases and inform design criteria for future therapies. Advisors/Committee Members: Jewell, Christopher M (advisor).

Subjects/Keywords: Biomedical engineering; Immunology; Materials Science; autoimmunity; biomaterial; immune tolerance; lymph node; microparticle; polyelectrolyte multilayers

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APA (6^th Edition):

Tostanoski, L. H. (2017). Engineering biomaterials to promote systemic, antigen-specific tolerance. (Thesis). University of Maryland. Retrieved from http://hdl.handle.net/1903/20276

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Tostanoski, Lisa Hoban. “Engineering biomaterials to promote systemic, antigen-specific tolerance.” 2017. Thesis, University of Maryland. Accessed January 16, 2021. http://hdl.handle.net/1903/20276.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Tostanoski, Lisa Hoban. “Engineering biomaterials to promote systemic, antigen-specific tolerance.” 2017. Web. 16 Jan 2021.

Vancouver:

Tostanoski LH. Engineering biomaterials to promote systemic, antigen-specific tolerance. [Internet] [Thesis]. University of Maryland; 2017. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/1903/20276.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Tostanoski LH. Engineering biomaterials to promote systemic, antigen-specific tolerance. [Thesis]. University of Maryland; 2017. Available from: http://hdl.handle.net/1903/20276

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Georgia

15. Rosenberg, Charles Stephen. The role of CD8+ T cell immunodominance in control of experimental Trypanosoma cruzi infection.

Degree: 2014, University of Georgia

URL: http://hdl.handle.net/10724/27287

► Trypanosoma cruzi infection drives the expansion of parasite-specific CD8+ T cells recognizing peptide epitopes encoded by trans-sialidase (TS) gene family members. The immunodominance of TS… (more)

▼ Trypanosoma cruzi infection drives the expansion of parasite-specific CD8+ T cells recognizing peptide epitopes encoded by trans-sialidase (TS) gene family members. The immunodominance of TS is remarkable; with up to 40% of all CD8+ T cells expressing T cell receptors recognizing the dominant TSKB20 and sub-dominant TSKB18 epitopes, these responses are among the strongest documented in any infection. However, mice fail to completely clear T. cruzi and subsequently develop chronic disease despite generating such highly focused T cell responses. Since T. cruzi’s genome encodes thousands of variant TS genes, we questioned the significance of these TS-specific CD8+ T cells. To determine the necessity of TS-specific CD8+ T cells for control of T. cruzi infection, we epitope-tolerized mice by injections of synthetic peptide epitopes. Mice tolerized to either the dominant or sub-dominant epitope, or both simultaneously, had transiently increased parasite burden though ultimately controlled acute infection, likely due to the activities of CD8+ T cells specific for unidentified parasite-derived epitopes. We hypothesized that these normally non-dominant CD8+ T cells could mediate long-term control of T. cruzi, so we developed transgenic mice expressing the TSKB20 or TSKB18 peptides as self-antigen to ensure central tolerance of peptide-specific CD8+ T cells. Recapitulating our previous findings, mice deleted of CD8+ T cells specific for TSKB20, TSKB18 or both peptides, were resistant to T. cruzi and developed functional effector CD8+ T cells. Mice deleted of the normally dominant CD8+ T cells controlled T. cruzi infection, but developed chronic infection and similar disease as their wild-type littermates. Though immunodomination by TS-specific T cells interferes with the development of responses targeting other parasite-encoded epitopes, deletion of the described dominant CD8+ T cells did not appear to enhance protective immunity nor change the outcome of infection. These data do not support a major role for TS-epitope immunodominance as a mechanism exploited by T. cruzi to promote the parasite’s persistence in the immune host, however, the data do indicate that strong responses against these TS-derived epitopes are non-essential. Furthermore, immunodominance by a particular CD8+ T cell population does not predict a critical role for that population in the control of T. cruzi infection.

Subjects/Keywords: Trypanosoma cruzi; Chagas disease; CD8+ T cell; immunodominance; immune evasion; tolerance; transgenic mouse

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APA (6^th Edition):

Rosenberg, C. S. (2014). The role of CD8+ T cell immunodominance in control of experimental Trypanosoma cruzi infection. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/27287

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Rosenberg, Charles Stephen. “The role of CD8+ T cell immunodominance in control of experimental Trypanosoma cruzi infection.” 2014. Thesis, University of Georgia. Accessed January 16, 2021. http://hdl.handle.net/10724/27287.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Rosenberg, Charles Stephen. “The role of CD8+ T cell immunodominance in control of experimental Trypanosoma cruzi infection.” 2014. Web. 16 Jan 2021.

Vancouver:

Rosenberg CS. The role of CD8+ T cell immunodominance in control of experimental Trypanosoma cruzi infection. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/10724/27287.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Rosenberg CS. The role of CD8+ T cell immunodominance in control of experimental Trypanosoma cruzi infection. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/27287

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

16. Salehipourshirazi, Golnaz. Cold-activation of the Drosophila melanogaster immune system.

Degree: 2013, University of Western Ontario

URL: https://ir.lib.uwo.ca/etd/1810

► Evidence of immune response enhancement after cold exposure suggests that cold activates the insect immune system. I investigated whether the immune response of Drosophila melanogaster… (more)

Subjects/Keywords: Cold tolerance; Immune system; Eco-immunology; cross-tolerance; Other Physiology

…effects on immune response and cold tolerance (Nilson et al., 2006). 2.2… …level of immune genes of Drosophila melanogaster females… …variance AMPs: Antimicrobial peptides CHC: Circulating hemocyte concentration IMD: Immune… …ecosystem. The immune system is one of the most important factors that affects insect survival… …x28;Kaya and Vega, 2012). Improving our knowledge of the insect immune system helps to…

7 more images…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Salehipourshirazi, G. (2013). Cold-activation of the Drosophila melanogaster immune system. (Thesis). University of Western Ontario. Retrieved from https://ir.lib.uwo.ca/etd/1810

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Salehipourshirazi, Golnaz. “Cold-activation of the Drosophila melanogaster immune system.” 2013. Thesis, University of Western Ontario. Accessed January 16, 2021. https://ir.lib.uwo.ca/etd/1810.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Salehipourshirazi, Golnaz. “Cold-activation of the Drosophila melanogaster immune system.” 2013. Web. 16 Jan 2021.

Vancouver:

Salehipourshirazi G. Cold-activation of the Drosophila melanogaster immune system. [Internet] [Thesis]. University of Western Ontario; 2013. [cited 2021 Jan 16]. Available from: https://ir.lib.uwo.ca/etd/1810.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Salehipourshirazi G. Cold-activation of the Drosophila melanogaster immune system. [Thesis]. University of Western Ontario; 2013. Available from: https://ir.lib.uwo.ca/etd/1810

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Florida

17. Posgai, Amanda L. Evaluating Efficacy and Mechanisms of Combination Therapies for the Prevention and Reversal of Type 1 Diabetes Using the Non-Obese Diabetic Mouse Model of the Disease.

Degree: PhD, Medical Sciences - Immunology and Microbiology (IDP), 2014, University of Florida

URL: https://ufdc.ufl.edu/UFE0047323

► Type 1 Diabetes (T1D) is characterized by the autoimmune destruction of the insulin-producing beta cells of the pancreatic islets leading to glycemic dysregulation which if… (more)

▼ Type 1 Diabetes (T1D) is characterized by the autoimmune destruction of the insulin-producing beta cells of the pancreatic islets leading to glycemic dysregulation which if left untreated, results in diabetic ketoacidosis-induced coma and eventually, death. While patients can learn to manage their condition with exogenous insulin, T1D often leads to severe systemic comorbidities, and to date, there is no available cure. In the past, monotherapies have successfully prevented, and even reversed T1D in the NOD mouse; however, none have proven effective in clinical trials. In many instances, this can be attributed to improper translation of drug dose or treatment regimen, and sometimes, the original findings are not replicable suggesting a need for more rigorous preclinical studies to optimize therapeutic protocols prior to clinical testing. The work detailed in this dissertation aimed to test combinations of candidate reagents for efficacy (in both the prevention and reversal settings) across multiple doses and treatment regimens using the NOD mouse model. In two experiments, we utilized novel transplastomic nicotine-free tobacco plants as vectors for oral protein delivery in prediabetic animals. The first study aimed to induce autoantigen-specific tolerance to glutamic acid decarboxylase and human proinsulin while the second sought to preserve beta cell mass via an incretin hormone, exendin 4, alone or in combination with oral autoantigen therapy, to prevent T1D onset. Two additional experiments were conducted in a multicenter preclinical consortium to test anti-CD20 + oral insulin and anti-CD3 + IL-1 blockade for the reversal of new-onset T1D. While studies of mechanism revealed limited evidence of subclinical immunological, histological, and gut microbial changes as markers of therapeutic effect, each of the therapies tested was unsuccessful in preventing or reversing disease. The oral route may not provide a robust avenue for tolerance induction in an autoimmune-prone host, particularly regarding self-antigen administration, and thus, may require additional combinatorial agents to address this problem. Our findings support the notion that there is a need for larger sample size, dose optimization, and attempts to verify original findings (at more than one institution if possible) in order to identify combination treatment(s) for translation to the clinic. ( en ) Advisors/Committee Members: ATKINSON,MARK A (committee chair), BRUSKO,TODD MICHAEL (committee member), TRIPLETT,ERIC (committee member), SONG,SIHONG (committee member).

Subjects/Keywords: Antigens; Autoantigens; Beta cells; Diabetes complications; Diseases; Immune tolerance; Insulin; Mice; Type 1 diabetes mellitus; Type 2 diabetes mellitus; autoimmune – diabetes – microbiome – nod – prevention – reversal – tolerance

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Posgai, A. L. (2014). Evaluating Efficacy and Mechanisms of Combination Therapies for the Prevention and Reversal of Type 1 Diabetes Using the Non-Obese Diabetic Mouse Model of the Disease. (Doctoral Dissertation). University of Florida. Retrieved from https://ufdc.ufl.edu/UFE0047323

Chicago Manual of Style (16^th Edition):

Posgai, Amanda L. “Evaluating Efficacy and Mechanisms of Combination Therapies for the Prevention and Reversal of Type 1 Diabetes Using the Non-Obese Diabetic Mouse Model of the Disease.” 2014. Doctoral Dissertation, University of Florida. Accessed January 16, 2021. https://ufdc.ufl.edu/UFE0047323.

MLA Handbook (7^th Edition):

Posgai, Amanda L. “Evaluating Efficacy and Mechanisms of Combination Therapies for the Prevention and Reversal of Type 1 Diabetes Using the Non-Obese Diabetic Mouse Model of the Disease.” 2014. Web. 16 Jan 2021.

Vancouver:

Posgai AL. Evaluating Efficacy and Mechanisms of Combination Therapies for the Prevention and Reversal of Type 1 Diabetes Using the Non-Obese Diabetic Mouse Model of the Disease. [Internet] [Doctoral dissertation]. University of Florida; 2014. [cited 2021 Jan 16]. Available from: https://ufdc.ufl.edu/UFE0047323.

Council of Science Editors:

Posgai AL. Evaluating Efficacy and Mechanisms of Combination Therapies for the Prevention and Reversal of Type 1 Diabetes Using the Non-Obese Diabetic Mouse Model of the Disease. [Doctoral Dissertation]. University of Florida; 2014. Available from: https://ufdc.ufl.edu/UFE0047323

18. Marshall, Heather D. Sensitization of CD8 T Cells During Acute Viral Infections Impacts Bystander and Latecomer CD8 T Cell Responses : A Dissertation.

Degree: Immunology and Microbiology, Pathology, 2009, U of Massachusetts : Med

URL: https://escholarship.umassmed.edu/gsbs_diss/440

► Many virus infections induce a transient state of immune suppression in the infected host. Virus-induced T cell suppression can be caused by T cell… (more)

▼ Many virus infections induce a transient state of immune suppression in the infected host. Virus-induced T cell suppression can be caused by T cell activation-induced cell death (AICD), dendritic cell (DC) apoptosis, DC dysfunction, and/or the enhanced expression of immune-suppressive cytokines. It has been previously demonstrated that naïve bystander CD8 T cells derived from hosts experiencing an acute virus-specific T cell response underwent AICD when polyclonally activated by anti-CD3 in vitro (Zarozinski et al., 2000). Susceptibility of naïve bystander T cells to AICD could prevent the development of a new T cell response during an ongoing immune response, and thus render infected hosts immune suppressed. Although immune suppression could result in an enhanced susceptibility to superinfections, virus-infected individuals are more commonly resistant to superinfecting pathogens. Because of these seemingly contradictory conditions, we sought to investigate how acute viral infections impact naïve bystander CD8 T cells in vivo. More specifically, we asked whether bystander CD8 T cells are susceptible to immune suppression or whether they can contribute to the resistance to superinfections. In order to address this, we examined the responses of bystander CD8 T cells activated with cognate antigen during acute viral infections in vivo. We generated several in vivomodels using P14 (LCMV glycoprotein-specific), HY (male antigen-specific), and OT-I (ovalbumin-specific) transgenic CD8 T cells, which we defined as bystander during acute infections with lymphocytic choriomeningitis virus (LCMV), Pichinde virus (PV), vaccinia virus (VV), and murine cytomegalovirus (MCMV). Consistent with the enhanced susceptibility to cell death noted in vitro, we found that bystander CD8 T cells activated with cognate antigen in vivo during acute viral infections underwent markedly reduced proliferation. Virus-induced transient T cell suppression in vivo was not exclusively mediated by Fas-FasL- or TNF-induced AICD or due to an enhanced susceptibility to apoptosis. Instead, immune suppression in vivowas associated with a delayed onset of division, which we found not to be due to a defect in antigen presentation, but rather due to a T cell intrinsic defect. Despite the suppressed proliferation of TCR-stimulated bystander CD8 T cells in vivo, we found an enhancement of the effector functions exerted by bystander CD8 T cells activated during acute viral infections. During acute viral infections or after stimulation with type 1 IFN (IFN-αβ) inducers, some bystander CD8 T cells were sensitized to immediately exert effector functions such as IFN-γ production and degranulation upon stimulation with high affinity cognate antigen. Sensitization of naïve CD8 T cells required self-MHC I and indirect effects of IFN-αβ, while IL-12, IL-18, and IFN-γ were not individually required. IL-15 was not required for the rapid expression of IFN-γ, but was required for… Advisors/Committee Members: Raymond M. Welsh, Ph.D..

Subjects/Keywords: Immune Tolerance; Bystander Effect; CD8-Positive T-Lymphocytes; Superinfection; Virus Diseases; Antigens; Viral; Bacterial Infections and Mycoses; Biological Factors; Cells; Hemic and Immune Systems; Parasitic Diseases; Virus Diseases

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Marshall, H. D. (2009). Sensitization of CD8 T Cells During Acute Viral Infections Impacts Bystander and Latecomer CD8 T Cell Responses : A Dissertation. (Doctoral Dissertation). U of Massachusetts : Med. Retrieved from https://escholarship.umassmed.edu/gsbs_diss/440

Chicago Manual of Style (16^th Edition):

Marshall, Heather D. “Sensitization of CD8 T Cells During Acute Viral Infections Impacts Bystander and Latecomer CD8 T Cell Responses : A Dissertation.” 2009. Doctoral Dissertation, U of Massachusetts : Med. Accessed January 16, 2021. https://escholarship.umassmed.edu/gsbs_diss/440.

MLA Handbook (7^th Edition):

Marshall, Heather D. “Sensitization of CD8 T Cells During Acute Viral Infections Impacts Bystander and Latecomer CD8 T Cell Responses : A Dissertation.” 2009. Web. 16 Jan 2021.

Vancouver:

Marshall HD. Sensitization of CD8 T Cells During Acute Viral Infections Impacts Bystander and Latecomer CD8 T Cell Responses : A Dissertation. [Internet] [Doctoral dissertation]. U of Massachusetts : Med; 2009. [cited 2021 Jan 16]. Available from: https://escholarship.umassmed.edu/gsbs_diss/440.

Council of Science Editors:

Marshall HD. Sensitization of CD8 T Cells During Acute Viral Infections Impacts Bystander and Latecomer CD8 T Cell Responses : A Dissertation. [Doctoral Dissertation]. U of Massachusetts : Med; 2009. Available from: https://escholarship.umassmed.edu/gsbs_diss/440

Université Montpellier II

19. Lapalud, Priscilla. Etude du répertoire épitopique et isotypique des anticorps anti-facteur VIII chez les patients atteints d'hémophilie A : Analysis of epitopic and isotypic profile of anti-FVIII antibodies in haemophilia A patients.

Degree: Docteur es, Biologie Santé, 2012, Université Montpellier II

URL: http://www.theses.fr/2012MON20173

►

Le facteur VIII (FVIII) joue un rôle essentiel dans la coagulation sanguine. Lorsque le FVIII fait génétiquement défaut, une pathologie hémorragique grave survient: l'hémophilie A… (more)

▼

Le facteur VIII (FVIII) joue un rôle essentiel dans la coagulation sanguine. Lorsque le FVIII fait génétiquement défaut, une pathologie hémorragique grave survient: l'hémophilie A (HA) congénitale. La complication majeure de la prise en charge de ces patients est l'apparition d'allo-anticorps (alloAcs) dirigés contre le FVIII thérapeutique administré. Dès lors, la seule thérapeutique efficace est l'induction de tolérance immune (ITI) qui vise à les éradiquer. Cependant, ce traitement échoue dans 30% des cas, sans qu'aucun facteur ne permette actuellement de prédire l'échec de ce traitement contraignant et coûteux. des facteurs immunologiques prédictifs de l'efficacité de l'ITI ont été recherchés chez 25 patients par analyse du répertoire épitopique et isotypique des Acs anti-FVIII à l'aide de la technologie x-MAP. Des biomarqueurs individuels (Acs anti-A2 et -A1 du FVIII), et des combinaisons originales ont été identifiés (0,841 < AUC < 0,946). Des manifestations hémorragiques peuvent apparaitre chez des patients non hémophiles, dues à des autoAcs anti-FVIII (HA acquise). Dans certains cas, les autoAcs se développent au moment du postpartum. peu de données sont disponibles sur cette réponse immune. Dans une seconde étude portant sur 73 cas, nous avons découvert un profil immunologique (autoAcs anti-A1) différenciant les HA du postpartum et les autres HA acquises. Les profils d'IgG anti-FVIII que nous avons établis s'avèrent prometteurs pour prédire l'efficacité de l'ITI et engendrer une cartographie précise de la réponse autoimmune chez les patients atteints d'HA acquise.

Factor VIII (FVIII) plays a critical role in blood coagulation. When FVIII s genetically defective, a serious hemorrhagic disease occurs: congenital hemophilia A (HA). The main complication of the management of these patients is the appearance of alloantibodies (alloAbs) directed against administred therapeutic FVIII. therefore, the only effective treatment is the immune tolerance induction (ITI), which aims to eradicate these alloAbs. However, this treatment fails in up to 30% of cases, without any factor currently able to predict the failure of this constraining and expensive treatment. Immunological factors predictive to the efficacy of ITI were investigated in 25 patients by analysis of epitopic and isotypic IgG profile of anti-FVIII Abs using x-MAP technology. Individual biomarkers (anti-FVIII A1 and -A2 Abs), and original combinations were identified (0,841 < AUC < 0,946). Hemorrhagic manifestations can occur in non-hemophiliac patients, due to anti-FVIII autoAbs (acquired HA). In some patients, the autoAbs appear in postpartum period but few data are available on the immune response due to the rarity of the disease. In a second study of 73 cases, we found a different immunological profile between patients with postpartum HA and the other acuired HA patients. IgG profiles of anti-FVIII we have established are promising for predicting the effectiveness of ITI and generate an accurate mapping of autoimmune response in patients with acquired…

Advisors/Committee Members: Lavigne, Géraldine (thesis director).

Subjects/Keywords: Anticorps anti-facteur VIII; Hémophiles A; Technologie x-MAP; Induction de tolérance immune; Postpartum; Anti-FVIII antibodies; Haemophilia A; X-MAP technology; Immune tolerance induction; Postpartum

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lapalud, P. (2012). Etude du répertoire épitopique et isotypique des anticorps anti-facteur VIII chez les patients atteints d'hémophilie A : Analysis of epitopic and isotypic profile of anti-FVIII antibodies in haemophilia A patients. (Doctoral Dissertation). Université Montpellier II. Retrieved from http://www.theses.fr/2012MON20173

Chicago Manual of Style (16^th Edition):

Lapalud, Priscilla. “Etude du répertoire épitopique et isotypique des anticorps anti-facteur VIII chez les patients atteints d'hémophilie A : Analysis of epitopic and isotypic profile of anti-FVIII antibodies in haemophilia A patients.” 2012. Doctoral Dissertation, Université Montpellier II. Accessed January 16, 2021. http://www.theses.fr/2012MON20173.

MLA Handbook (7^th Edition):

Lapalud, Priscilla. “Etude du répertoire épitopique et isotypique des anticorps anti-facteur VIII chez les patients atteints d'hémophilie A : Analysis of epitopic and isotypic profile of anti-FVIII antibodies in haemophilia A patients.” 2012. Web. 16 Jan 2021.

Vancouver:

Lapalud P. Etude du répertoire épitopique et isotypique des anticorps anti-facteur VIII chez les patients atteints d'hémophilie A : Analysis of epitopic and isotypic profile of anti-FVIII antibodies in haemophilia A patients. [Internet] [Doctoral dissertation]. Université Montpellier II; 2012. [cited 2021 Jan 16]. Available from: http://www.theses.fr/2012MON20173.

Council of Science Editors:

Lapalud P. Etude du répertoire épitopique et isotypique des anticorps anti-facteur VIII chez les patients atteints d'hémophilie A : Analysis of epitopic and isotypic profile of anti-FVIII antibodies in haemophilia A patients. [Doctoral Dissertation]. Université Montpellier II; 2012. Available from: http://www.theses.fr/2012MON20173

20. Espinosa Carrasco, Gabriel. L'activation des cellules T CD8+ et T CD4+ en réponse aux auto-antigènes : du tissu lymphoïde à l'organe cible : Activation of CD8+ and CD4+ T cells in response to self-antigen : from the lymphoid tissue to the target organ.

Degree: Docteur es, Biologie Santé, 2016, Montpellier

URL: http://www.theses.fr/2016MONTT026

►

Le système immunitaire comporte différents mécanismes de tolérance périphérique permettant de contrôler la réponse des cellules T CD8+. Dans certaines conditions encore peu connues, des… (more)

▼

Le système immunitaire comporte différents mécanismes de tolérance périphérique permettant de contrôler la réponse des cellules T CD8+. Dans certaines conditions encore peu connues, des cellules T potentiellement auto-réactives peuvent contourner les mécanismes de tolérance et se différencier en cellules effectrices, capables d’attaquer différentes organes de l’organisme, dans un processus d’auto-réactivité. En utilisant une souris transgénique exprimant un antigène modèle dans les cellules bêta du pancréas, j’ai étudié deux processus fondamentaux impliqués dans la différenciation des cellules T CD8+ en réponse aux antigènes du soi.1) Rôle de la translocation des lipopolysaccharides (LPS) dans la rupture de la tolérance. Nous avons préalablement démontré dans le laboratoire que des protocoles de lympho-déplétions, tels l’irradiation, étaient capables d’induire une rupture de la tolérance périphérique dans les cellules T CD8+. L’irradiation provoque la translocation des LPS des bactéries commensales vers la circulation sanguine, ce qui induit une activation du système immunitaire inné. Mes données ont montré que la translocation des LPS était corrélée avec l’activation systémique des cellules dendritiques (DC) CD11c+, en particulier les DC CD8+, responsables de la cross-présentation des auto-antigènes pancréatiques dans les tissus lymphoïdes. Alors que le traitement par des antibiotiques avant l’irradiation permet de prévenir la translocation des LPS, l’activation des DC n’est que partiellement affectée, et le développement de l’auto-immunité résultant d’une rupture de la tolérance périphérique des cellules T CD8+ ne peut pas être empêchée par le traitement.2) Visualisation de la coopération entre cellules T CD4+ et CD8+ effectrices dans la destruction des cellules bêta pancréatiques in vivo. En utilisant la microscopie intra-vitale à 2-photons, j’ai pu analyser, pour la première fois, la dynamiques des cellules T CD4+ et CD8+ auto-réactives exprimant un marqueur fluorescent, lors de l’infiltration du pancréas et du développement du diabète auto-immun. J’ai mis en évidence que l’infiltration des cellules T était accompagnée d’un remodelage de la matrice extracellulaire du pancréas, permettant la migration dirigée des lymphocytes. De plus, j’ai montré que l’arrêt MHC classe II-dépendant des cellules T CD4+, dû à des interactions avec des cellules présentatrices d’antigène recrutées au site d’inflammation et impliquant dans certains cas également les cellules T CD8+, contribuait au maintien des fonctions effectrices des cellules T CD8+.

The immune system has evolved multiple mechanisms of peripheral tolerance to control CD8+ T cell responses. Under particular conditions that are not yet well understood, potentially autoreactive T cells may override tolerance and differentiate into effector cells capable of targeting the own components of the organism resulting in self-reactivity. Utilizing transgenic mice expressing a model antigen in the beta cells of the pancreas, I have studied two important processes involved in…

Advisors/Committee Members: Hernandez, Javier (thesis director).

Subjects/Keywords: Tolérance immune; Auto-Immunité; Lymphocyte T CD8+; Lymphocyte T CD4+; Microscopie intra-Vitale; Immune Tolerance; Autoimmunity; CD8+ T cytotoxic cell; CD4+ T helper cell; Intra-Vital imaging

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Espinosa Carrasco, G. (2016). L'activation des cellules T CD8+ et T CD4+ en réponse aux auto-antigènes : du tissu lymphoïde à l'organe cible : Activation of CD8+ and CD4+ T cells in response to self-antigen : from the lymphoid tissue to the target organ. (Doctoral Dissertation). Montpellier. Retrieved from http://www.theses.fr/2016MONTT026

Chicago Manual of Style (16^th Edition):

Espinosa Carrasco, Gabriel. “L'activation des cellules T CD8+ et T CD4+ en réponse aux auto-antigènes : du tissu lymphoïde à l'organe cible : Activation of CD8+ and CD4+ T cells in response to self-antigen : from the lymphoid tissue to the target organ.” 2016. Doctoral Dissertation, Montpellier. Accessed January 16, 2021. http://www.theses.fr/2016MONTT026.

MLA Handbook (7^th Edition):

Espinosa Carrasco, Gabriel. “L'activation des cellules T CD8+ et T CD4+ en réponse aux auto-antigènes : du tissu lymphoïde à l'organe cible : Activation of CD8+ and CD4+ T cells in response to self-antigen : from the lymphoid tissue to the target organ.” 2016. Web. 16 Jan 2021.

Vancouver:

Espinosa Carrasco G. L'activation des cellules T CD8+ et T CD4+ en réponse aux auto-antigènes : du tissu lymphoïde à l'organe cible : Activation of CD8+ and CD4+ T cells in response to self-antigen : from the lymphoid tissue to the target organ. [Internet] [Doctoral dissertation]. Montpellier; 2016. [cited 2021 Jan 16]. Available from: http://www.theses.fr/2016MONTT026.

Council of Science Editors:

Espinosa Carrasco G. L'activation des cellules T CD8+ et T CD4+ en réponse aux auto-antigènes : du tissu lymphoïde à l'organe cible : Activation of CD8+ and CD4+ T cells in response to self-antigen : from the lymphoid tissue to the target organ. [Doctoral Dissertation]. Montpellier; 2016. Available from: http://www.theses.fr/2016MONTT026

21. Jansen, M.A.A. Tuning tolerance : Modulating adaptive immune responses for therapeutic purposes.

Degree: 2019, University Utrecht

URL: https://dspace.library.uu.nl/handle/1874/374622 ; URN:NBN:NL:UI:10-1874-374622 ; 1874/374622 ; urn:isbn:9789039370735 ; URN:NBN:NL:UI:10-1874-374622 ; https://dspace.library.uu.nl/handle/1874/374622

► Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation in the joints, leading to pain, stiffness and cartilage damage. Immune regulatory failure or… (more)

▼ Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation in the joints, leading to pain, stiffness and cartilage damage. Immune regulatory failure or imbalance in anti- and pro-inflammatory responses could lead towards autoimmune diseases. However, the initial trigger that causes this faulty immune regulation is often unknown which is also the case in RA. Therefore, it is not possible yet to treat the initiation of disease in an antigen specific way, which means that current medication is directed towards relief of symptoms. To cure disease, restoring immune tolerance is required. For this reason, therapies that restore the immune balance are being explored. In this thesis we investigated two possible approaches: tolerogenic dendritic cells and nanoparticles containing TNF siRNA. Tolerogenic dendritic cells Dendritic cells (DCs) are important players in the immune system for their ability to activate and dampen the immune system. DCs can be modulated in the laboratory into tolerogenic dendritic cells (tolDCs), these tolDCs could restore immune tolerance. In this thesis, we have shown that tolDCs, induced by dexamethasone and 1,25-dihydroxyvitamin D3, do not induce new regulatory T cells but dampen the activation and proliferation of CD4+ T cells. This results in overall more Tregs and an immune-regulatory state. Since the autoantigen in RA is unknown, we sought possible alternative autoantigens. We investigated HSPs as possible surrogate autoantigens. Since roughly eighty percent of both healthy donors and inflammatory arthritis patients showed a CD4+ T cellresponse towards HSPs, we reasoned that HSPs could be used to modulate CD4+ T cell responses in humans. Furthermore, tolDCs pulsed with HSP or control peptides induced a Tr1 phenotype in the CD4+ T cells. Nanoparticles TNF is a pro-inflammatory cytokine that plays an important role in the pathogenesis of RA. RNA interference therapy could be a solution to inhibit excessive TNF production and dampen inflammation in RA. However, to get TNF siRNA across the cell membrane a drug delivery system such as nanoparticles are needed. Especially in autoimmunity, the delivery system itself should not induce any additional (pro-inflammatory) immune responses. Two nanoparticle types were designed to deliver TNF siRNA without extra immune activation. After showing that TNF siRNA is able to inhibit TNF production in a macrophage cell line, we tested the nanoparticles in an in vivo experimental arthritis model. Both the nanoparticle types containing TNF siRNA restrained arthritic symptoms after local administration, indicating that TNF was silenced in vivo. Since the route of administration of these tolerogenic therapies can influence the outcome, we compared two non-traditional routes (intradermal and intranasal) of vaccination. We noticed differences in immune cell activation and cytokine production, which illustrates that the micromilieu and immune response differ greatly between the several administration routes. The results described in this… Advisors/Committee Members: van Eden, Willem, Broere, Femke.

Subjects/Keywords: Immune tolerance; Rheumatoid arthritis; tolDC; nanoparticle; vaccination; autoimmunity; immune modulation

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APA (6^th Edition):

Jansen, M. A. A. (2019). Tuning tolerance : Modulating adaptive immune responses for therapeutic purposes. (Doctoral Dissertation). University Utrecht. Retrieved from https://dspace.library.uu.nl/handle/1874/374622 ; URN:NBN:NL:UI:10-1874-374622 ; 1874/374622 ; urn:isbn:9789039370735 ; URN:NBN:NL:UI:10-1874-374622 ; https://dspace.library.uu.nl/handle/1874/374622

Chicago Manual of Style (16^th Edition):

Jansen, M A A. “Tuning tolerance : Modulating adaptive immune responses for therapeutic purposes.” 2019. Doctoral Dissertation, University Utrecht. Accessed January 16, 2021. https://dspace.library.uu.nl/handle/1874/374622 ; URN:NBN:NL:UI:10-1874-374622 ; 1874/374622 ; urn:isbn:9789039370735 ; URN:NBN:NL:UI:10-1874-374622 ; https://dspace.library.uu.nl/handle/1874/374622.

MLA Handbook (7^th Edition):

Jansen, M A A. “Tuning tolerance : Modulating adaptive immune responses for therapeutic purposes.” 2019. Web. 16 Jan 2021.

Vancouver:

Jansen MAA. Tuning tolerance : Modulating adaptive immune responses for therapeutic purposes. [Internet] [Doctoral dissertation]. University Utrecht; 2019. [cited 2021 Jan 16]. Available from: https://dspace.library.uu.nl/handle/1874/374622 ; URN:NBN:NL:UI:10-1874-374622 ; 1874/374622 ; urn:isbn:9789039370735 ; URN:NBN:NL:UI:10-1874-374622 ; https://dspace.library.uu.nl/handle/1874/374622.

Council of Science Editors:

Jansen MAA. Tuning tolerance : Modulating adaptive immune responses for therapeutic purposes. [Doctoral Dissertation]. University Utrecht; 2019. Available from: https://dspace.library.uu.nl/handle/1874/374622 ; URN:NBN:NL:UI:10-1874-374622 ; 1874/374622 ; urn:isbn:9789039370735 ; URN:NBN:NL:UI:10-1874-374622 ; https://dspace.library.uu.nl/handle/1874/374622

22. Langlais, Carly L. Rhesus rhadinovirus encodes a functional homologue of human CD200.

Degree: PhD, 2005, Oregon Health Sciences University

URL: doi:10.6083/M4C827JT ; http://digitalcommons.ohsu.edu/etd/2946

Subjects/Keywords: Rhadinovirus; Macaca mulatta; Antigens, CD; Down-Regulation; Immune Tolerance

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Langlais, C. L. (2005). Rhesus rhadinovirus encodes a functional homologue of human CD200. (Doctoral Dissertation). Oregon Health Sciences University. Retrieved from doi:10.6083/M4C827JT ; http://digitalcommons.ohsu.edu/etd/2946

Chicago Manual of Style (16^th Edition):

Langlais, Carly L. “Rhesus rhadinovirus encodes a functional homologue of human CD200.” 2005. Doctoral Dissertation, Oregon Health Sciences University. Accessed January 16, 2021. doi:10.6083/M4C827JT ; http://digitalcommons.ohsu.edu/etd/2946.

MLA Handbook (7^th Edition):

Langlais, Carly L. “Rhesus rhadinovirus encodes a functional homologue of human CD200.” 2005. Web. 16 Jan 2021.

Vancouver:

Langlais CL. Rhesus rhadinovirus encodes a functional homologue of human CD200. [Internet] [Doctoral dissertation]. Oregon Health Sciences University; 2005. [cited 2021 Jan 16]. Available from: doi:10.6083/M4C827JT ; http://digitalcommons.ohsu.edu/etd/2946.

Council of Science Editors:

Langlais CL. Rhesus rhadinovirus encodes a functional homologue of human CD200. [Doctoral Dissertation]. Oregon Health Sciences University; 2005. Available from: doi:10.6083/M4C827JT ; http://digitalcommons.ohsu.edu/etd/2946

23. Lepiller, Quentin. Rôle de l'indoléamine-2,3-dioxygénase dans la persistance des infections virales : Role of indoleamine-2,3-dioxygenase in chronic viral infections.

Degree: Docteur es, Aspects moléculaires et cellulaires de la biologie, 2015, Université de Strasbourg

URL: http://www.theses.fr/2015STRAJ008

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L’indoléamine-2,3-dioxygénase (IDO) est une enzyme du catabolisme du tryptophane suspectée de jouer un double rôle lors des infections en contribuant aux défenses innées de l’hôte… (more)

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L’indoléamine-2,3-dioxygénase (IDO) est une enzyme du catabolisme du tryptophane suspectée de jouer un double rôle lors des infections en contribuant aux défenses innées de l’hôte et en régulant la réponse immunitaire. IDO est exprimée au cours de l’infection par le virus de l’hépatite C (VHC). Cependant, les mécanismes moléculaires conduisant à l’expression de IDO lors de l’hépatite C et l’impact de IDO sur la réplication virale et sur la réponse immunitaire ne sont pas connus. Dans ce travail de thèse, nous avons montré que le VHC stimule l’expression de IDO dans les hépatocytes.L’expression de IDO était transitoire et coïncidait avec l’expression des interférons (IFNs) de types I et III et avec la transcription de gènes stimulés par les IFNs. L’expression de IDO était également augmentée dans les hépatocytes exposés à la présence de lymphocytes T CD4+ activés et producteurs d’IFN-γ. L’expression hépatique de IDO diminuait la réplication virale, ce qui suggère que IDO limite la diffusion du VHC dans le foie au cours de l’hépatite C. Grâce à des expériences de silencing, nous avons montré que IDO contribue à l’effet antiviral de l’IFN-α sur le VHC. L’expression de IDO était régulée par l’activation des facteurs de transcription IRF-1 et STAT-1 dans les hépatocytes infectés par le VHC. En plus de son effet antiviral sur le VHC, l’expression hépatique de IDO inhibait significativement la prolifération des lymphocytes T CD4+ activés, suggérant un rôle immunorégulateur de IDO au cours de l’hépatite C. Nos données suggèrent donc que IDO joue un double jeu lors de l’hépatite C, en limitant la réplication virale et en régulant la réponse immunitaire adaptative de l’hôte. Notre travail ouvre la voie à des expérimentations in vivo et à des études cliniques visant à préciser la place des inhibiteurs pharmacologiques de IDO dans l’arsenal thérapeutique contre le VHC.

Indoleamine-2,3-dioxygenase (IDO) is a tryptophan-catabolizing enzyme that plays a dual role during infectious diseases by contributing to the innate defenses against pathogens and by regulating the immune response. IDO is expressed in patients with hepatitis C virus (HCV) infection. However, the molecular mechanism of IDO induction in HCV infection and its role in the antiviral immune response remain unknown. Using primary human hepatocytes, we have shown that HCV infection stimulates IDO expression. IDO gene induction was transient and coincided with the expression of type I and type III interferons (IFNs) and IFN-stimulated genes (ISGs) in HCV-infected hepatocytes. IDO expression was also stimulated when the hepatocytes were incubated with IFN-γ-secreting CD4+ T cells. Expression of IDO prior to HCV infection significantly impaired HCV replication in hepatocytes, suggesting that IDO limits the spread of HCV in the liver. By using siRNA-mediated IDO knockdown experiments, we have shown that IDO contributes to the IFN-α-antiviral effect on HCV replication. IDO expression was regulated by IRF-1 and STAT-1 in HCV-infected hepatocytes. Hepatic IDO expression also…

Advisors/Committee Members: Barth, Heidi (thesis director).

Subjects/Keywords: Indoléamine-2,3-dioxygénase; VHC; Immunité innée; Tolérance immunitaire; Indoleamine-2,3-dioxygenase; HCV; Innate immunity; Immune tolerance; 571.96; 616.91

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lepiller, Q. (2015). Rôle de l'indoléamine-2,3-dioxygénase dans la persistance des infections virales : Role of indoleamine-2,3-dioxygenase in chronic viral infections. (Doctoral Dissertation). Université de Strasbourg. Retrieved from http://www.theses.fr/2015STRAJ008

Chicago Manual of Style (16^th Edition):

Lepiller, Quentin. “Rôle de l'indoléamine-2,3-dioxygénase dans la persistance des infections virales : Role of indoleamine-2,3-dioxygenase in chronic viral infections.” 2015. Doctoral Dissertation, Université de Strasbourg. Accessed January 16, 2021. http://www.theses.fr/2015STRAJ008.

MLA Handbook (7^th Edition):

Lepiller, Quentin. “Rôle de l'indoléamine-2,3-dioxygénase dans la persistance des infections virales : Role of indoleamine-2,3-dioxygenase in chronic viral infections.” 2015. Web. 16 Jan 2021.

Vancouver:

Lepiller Q. Rôle de l'indoléamine-2,3-dioxygénase dans la persistance des infections virales : Role of indoleamine-2,3-dioxygenase in chronic viral infections. [Internet] [Doctoral dissertation]. Université de Strasbourg; 2015. [cited 2021 Jan 16]. Available from: http://www.theses.fr/2015STRAJ008.

Council of Science Editors:

Lepiller Q. Rôle de l'indoléamine-2,3-dioxygénase dans la persistance des infections virales : Role of indoleamine-2,3-dioxygenase in chronic viral infections. [Doctoral Dissertation]. Université de Strasbourg; 2015. Available from: http://www.theses.fr/2015STRAJ008

24. Bianchi, Pedro Kastein Faria da Cunha. Fenotipagem das células indoleamina 2,3 dioxigenase - IDO positivas em cultura de células placentárias e embrionárias de ratas Wistar sob influência do INF-γ e da progesterona.

Degree: Mestrado, Anatomia dos Animais Domésticos e Silvestres, 2013, University of São Paulo

URL: http://www.teses.usp.br/teses/disponiveis/10/10132/tde-11082014-115503/ ;

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A gestação confere ao organismo materno uma série de mudanças e desafios, envolvendo especialmente seu sistema imunológico. O feto, do ponto de vista imunológico, é… (more)

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A gestação confere ao organismo materno uma série de mudanças e desafios, envolvendo especialmente seu sistema imunológico. O feto, do ponto de vista imunológico, é comparado a um enxerto semi-alogenêico, pois expressa moléculas do complexo de histocompatibilidade principal (MHC) paterno, considerado não próprio ao organismo materno, capaz de desencadear uma resposta imunológica no ambiente intrauterino. Porém, durante todo o período gestacional, o organismo materno reconhece o embrião sem uma resposta imunológica contra sua permanência no útero, estabelecendo-se uma tolerância materno-fetal. Vários mecanismos contribuem para esse estado tolerogênico, como a atividade da enzima indoleamina 2,3-dioxigenase (IDO). A IDO promove o catabolismo do aminoácido triptofano, levando as células T à apoptose, devido à carência deste aminoácido e pela ação de seus catabólitos no micro ambiente placentário. Diversos tipos celulares estão presentes na interface materno fetal e vários deles podem potencialmente expressar a IDO. Em ratas Wistar, sabe-se que diversas proteínas, principalmente o interferon γ e, recentemente, a progesterona, podem aumentar a expressão desta enzima; contudo, ainda não são conhecidos quais tipos celulares são efetivamente influenciados por estas moléculas. Desta forma, este trabalho buscou suprir esta lacuna, por meio da identificação das células IDO positivas pela imunofenotipagem e citometria de fluxo. De acordo com as analises realizadas, os resultados deste trabalho mostraram que todos os tipos celulares fenotipados foram capazes de expressar a enzima. Contudo somente alguns grupos específicos de células presentes no ambiente uterino placentário sofrem influência das proteínas supracitadas, principalmente as células dendríticas, e os linfócitos CD4 que elevam a expressão de IDO na presença de progesterona e IFN-γ. Tais achados sugerem que a ação da enzima em grupos celulares específicos poderiam constituir meios pelo qual o organismo regula o sistema imunológico no ambiente uterino-placentário, em que é capaz de impedir o desenvolvimento de células imunológicas potencialmente ativas, colaborando com a formação de um ambiente tolerogênico favorável para o desenvolvimento embrionário.

Pregnancy causes several changes and challenges to the maternal body, especially involving the immune system. The fetus, on the immunological point of view, is compared to a semialogeneic graft, expressed as molecules of the paternal major histocompatibility complex (MHC) considered not self to the maternal organism, capable of triggering an immune response in the intrauterine environment. However, throughout the gestational period, maternal organism tolerates the embryo without an immune response against its permanence in the uterus, establishing maternal-fetal tolerance. Several mechanisms contribute to this tolerogenic state, as the activity of the enzyme indoleamine 2,3-dioxygenase (IDO). The IDO promotes the catabolism of tryptophan, inducing T cells apoptosis due to the deprivation of this amino acid…

Advisors/Committee Members: Kfoury Junior, José Roberto.

Subjects/Keywords: Immune system; Indoleamina 2,; 3 dioxigenase; Indoleamine 2,; 3 dioxygenase; Maternal-fetal tolerance; Sistema imunológico; Tolerância materno-fetal; Triptofano; Tryptophan

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bianchi, P. K. F. d. C. (2013). Fenotipagem das células indoleamina 2,3 dioxigenase - IDO positivas em cultura de células placentárias e embrionárias de ratas Wistar sob influência do INF-γ e da progesterona. (Masters Thesis). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/10/10132/tde-11082014-115503/ ;

Chicago Manual of Style (16^th Edition):

Bianchi, Pedro Kastein Faria da Cunha. “Fenotipagem das células indoleamina 2,3 dioxigenase - IDO positivas em cultura de células placentárias e embrionárias de ratas Wistar sob influência do INF-γ e da progesterona.” 2013. Masters Thesis, University of São Paulo. Accessed January 16, 2021. http://www.teses.usp.br/teses/disponiveis/10/10132/tde-11082014-115503/ ;.

MLA Handbook (7^th Edition):

Bianchi, Pedro Kastein Faria da Cunha. “Fenotipagem das células indoleamina 2,3 dioxigenase - IDO positivas em cultura de células placentárias e embrionárias de ratas Wistar sob influência do INF-γ e da progesterona.” 2013. Web. 16 Jan 2021.

Vancouver:

Bianchi PKFdC. Fenotipagem das células indoleamina 2,3 dioxigenase - IDO positivas em cultura de células placentárias e embrionárias de ratas Wistar sob influência do INF-γ e da progesterona. [Internet] [Masters thesis]. University of São Paulo; 2013. [cited 2021 Jan 16]. Available from: http://www.teses.usp.br/teses/disponiveis/10/10132/tde-11082014-115503/ ;.

Council of Science Editors:

Bianchi PKFdC. Fenotipagem das células indoleamina 2,3 dioxigenase - IDO positivas em cultura de células placentárias e embrionárias de ratas Wistar sob influência do INF-γ e da progesterona. [Masters Thesis]. University of São Paulo; 2013. Available from: http://www.teses.usp.br/teses/disponiveis/10/10132/tde-11082014-115503/ ;

25. Lago, Fernanda. Perfil imunoistoquímico de linfócitos T regulatórios no pênfico foliáceo endêmico através da expressão do marcador Foxp3.

Degree: PhD, Dermatologia, 2011, University of São Paulo

URL: http://www.teses.usp.br/teses/disponiveis/5/5133/tde-01122011-194907/ ;

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Introdução: Os linfócitos T regulatórios CD4+CD25+Foxp3+ (Tregs) desempenham um papel fundamental na manutenção da tolerância aos antígenos próprios e no controle da magnitude da resposta… (more)

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Introdução: Os linfócitos T regulatórios CD4+CD25+Foxp3+ (Tregs) desempenham um papel fundamental na manutenção da tolerância aos antígenos próprios e no controle da magnitude da resposta imunológica. Alterações quantitativas ou funcionais foram descritas em diversos distúbios auto-imunes. O pênfigo foliáceo endêmico (PFE) é uma doença bolhosa cutânea de natureza auto-imune, que compartilha características clínicas e imunopatológicas com o pênfigo foliáceo clássico, mas apresenta achados epidemiológicos próprios. Auto-anticorpos circulantes e teciduais da classe IgG dirigidos contra caderinas desmossômicas (desmogleína 1), levam à perda de adesão entre os queratinócitos. Objetivo: O objetivo deste estudo foi avaliar se a perda de tolerância é associada com alterações quantitativas nos linfócitos Tregs CD4+CD25+Foxp3+ na pele de pacientes com PFE. Métodos: Amostras de pele de 22 pacientes e 10 controles saudáveis foram submetidos à análise imunoistoquímica com anti-CD4, anti-CD25 e anti-Foxp3. Fotomicrografias foram obtidas de campos consecutivos ao longo de toda epiderme e derme. A seguir, foi realizada quantificação dos linfócitos Foxp3+, CD4+, CD25+, CD4+Foxp3+ e CD25+Foxp3+ em cada compartimento, considerando-se a respectiva área de cada campo (m2). Valores significantemente estatísticos foram considerados como p<0,05. Resultados: Encontramos um infiltrado epidérmico aumentado de linfócitos imunomarcados CD25+(p=0,003), Foxp3+(p=0,04) e CD25+Foxp3+ (p=0,007), em comparação com os controles. O infiltrado dérmico exibiu uma maior expressão de linfócitos CD4+ (p<0,001) e CD25+ (p=0,008) em amostras de pele de pacientes com PFE, quando comparados aos controles. Conclusões: Nossos achados sugerem que a quebra de tolerância imunológica periférica nos pacientes com PFE não se correlaciona com uma diminuição dos linfócitos T reg CD4+CD25+Foxp3+ na pele afetada. Entretanto, uma maior expressão de linfócitos CD25+Foxp3+ no infiltrado epidérmico poderia representar outra população de linfócitos com atividade regulatória, a ser definida.

Background: CD4+CD25+Foxp3+ regulatory T cells (Tregs) play a crucial role in the maintenance of self tolerance and control of the magnitude of the immune response. Their quantitative or functional impairment has been reported in several autoimmune disorders. Endemic pemphigus foliaceus (EPF) is an autoimmune organ-specific blistering skin disorder that shares many clinical and immunopathological features with classic pemphigus foliaceus, but with unique epidemiological features. Circulating and tissue-bound IgG auto-antibodies react against desmosomal cadherins (desmoglein 1), causing loss of adhesion between keratinocytes. Aims: The purpose of this study was to evaluate whether the loss of tolerance is associated with impairment of CD4+CD25+Foxp3+ Tregs in the skin of EPF patients. Methods: Skin samples from 22 patients and 10 controls were submitted to immunohistochemistry with anti-CD4, CD25 and Foxp3. Photomicrographs were obtained from consecutive fields along epidermis and dermis;…

Advisors/Committee Members: Aoki, Valeria.

Subjects/Keywords: Auto-imunidade; Autoimmunity; Foxp3; Foxp3; Immune tolerance; Linfócitos T reguladores; Pemphigus; Pênfigo; T-lymphocytes regulatory; Tolerância imunológica

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lago, F. (2011). Perfil imunoistoquímico de linfócitos T regulatórios no pênfico foliáceo endêmico através da expressão do marcador Foxp3. (Doctoral Dissertation). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/5/5133/tde-01122011-194907/ ;

Chicago Manual of Style (16^th Edition):

Lago, Fernanda. “Perfil imunoistoquímico de linfócitos T regulatórios no pênfico foliáceo endêmico através da expressão do marcador Foxp3.” 2011. Doctoral Dissertation, University of São Paulo. Accessed January 16, 2021. http://www.teses.usp.br/teses/disponiveis/5/5133/tde-01122011-194907/ ;.

MLA Handbook (7^th Edition):

Lago, Fernanda. “Perfil imunoistoquímico de linfócitos T regulatórios no pênfico foliáceo endêmico através da expressão do marcador Foxp3.” 2011. Web. 16 Jan 2021.

Vancouver:

Lago F. Perfil imunoistoquímico de linfócitos T regulatórios no pênfico foliáceo endêmico através da expressão do marcador Foxp3. [Internet] [Doctoral dissertation]. University of São Paulo; 2011. [cited 2021 Jan 16]. Available from: http://www.teses.usp.br/teses/disponiveis/5/5133/tde-01122011-194907/ ;.

Council of Science Editors:

Lago F. Perfil imunoistoquímico de linfócitos T regulatórios no pênfico foliáceo endêmico através da expressão do marcador Foxp3. [Doctoral Dissertation]. University of São Paulo; 2011. Available from: http://www.teses.usp.br/teses/disponiveis/5/5133/tde-01122011-194907/ ;

26. Dias, Renata Helena Ferreira Caramez Pierroni. Análise do fenômeno da imunotolerância na fotocarcinogênese em lábio.

Degree: Mestrado, Patologia Bucal, 2011, University of São Paulo

URL: http://www.teses.usp.br/teses/disponiveis/23/23141/tde-06032012-165809/ ;

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A radiação ultravioleta (UV) do sol é a principal responsável pelo desenvolvimento do câncer de pele não-melanoma. A radiação UV induz efeitos biológicos, que promovem… (more)

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A radiação ultravioleta (UV) do sol é a principal responsável pelo desenvolvimento do câncer de pele não-melanoma. A radiação UV induz efeitos biológicos, que promovem a fotocarcinogênese, agindo diretamente sobre o DNA, provocando mutações. Porém, tudo indica que há um efeito indireto, que induz imunossupressão. O fenômeno fisiológico da imunotolerância, que é responsável pela prevenção de doenças autoimunes e pela modulação da resposta inflamatória, pode ser aproveitado por determinadas neoplasias para escaparem do controle imunológico e reforçado pela radiação UV. Os personagens principais da imunotolerância no ambiente tumoral são células dendríticas imaturas e linfócitos T reguladores (Treg), além de inúmeras citocinas imunossupressoras. Com o objetivo de avaliar a imunotolerância na fotocarcinogênese em lábio, foram analisadas, por meio da técnica de imuno-histoquímica, 75 amostras de material fixado e emblocado em parafina, sendo 44 casos de queilite actínica (QA) nos três graus de displasia epitelial (discreta, moderada e intensa), 18 casos de carcinoma epidermoide de lábio (CEL) e 12 espécimes representativos de lábio normal (LN). Tais amostras foram submetidas aos anticorpos anti-CD83, anti-DEC-205, anti-FOXP3, anti-CD1a e anti-CD207. Foi efetuada a contagem de células em 3 campos significativos, escolhidos aleatoriamente, e obtida a média de células contadas/campo. Assim, os resultados mostraram uma grande quantia de linfócitos Treg FOXP3+ tanto no CEL como na QA. Também houve uma expressão acentuada de DEC-205 nos casos estudados. Quanto à presença de células de Langerhans CD207+ e CD1a+, notou-se um acúmulo no epitélio das lesões de QA e nas ilhotas do CEL, além de algumas células estarem presentes no tecido conjuntivo. Já para o marcador CD83, a contagem de células positivas foi baixa em relação aos demais marcadores tanto no CEL como na QA. Portanto, sugere-se um microambiente imunotolerante tanto no início, quanto no estabelecimento do processo da fotocarcinogênese em lábio.

Ultraviolet radiation (UV) is the main cause of non-melanoma skin cancer and induces biological effects that promote photocarcinogenesis by causing mutations directly on DNA. However, there seems to be an indirect effect, which induces immunosuppession. The physiological phenomenon of immune tolerance, which is responsible for the prevention of autoimmune diseases and the modulation of inflammatory response, may be used by certain tumors to escape immune control. This phenomenon is enhanced by UV radiation. Immature dendritic cells, regulatory T cells (Treg), and also several immunosuppressive cytokines play a central role in immune tolerance associated to the tumor environment. In order to assess the immune tolerance in lip photocarcinogenesis, we analyzed 75 samples represented by 44 cases of actinic cheilitis (AC), 18 cases of lip squamous cell carcinoma (LSCC) and 12 specimens of normal lip. Sections were submitted by means of immunohistochemistry, to the antibodies against CD83, DEC-205, FOXP3, CD1a and CD207. Positive…

Advisors/Committee Members: Martins, Marília Trierveiler.

Subjects/Keywords: Actinic cheilitis; Carcinoma de células escamosas; Células de Langerhans; Fotocarcinogênese; Immune tolerance; Langerhans cells; Queilite actínica; Squamous cell carcinoma; Tolerância imunológica

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Dias, R. H. F. C. P. (2011). Análise do fenômeno da imunotolerância na fotocarcinogênese em lábio. (Masters Thesis). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/23/23141/tde-06032012-165809/ ;

Chicago Manual of Style (16^th Edition):

Dias, Renata Helena Ferreira Caramez Pierroni. “Análise do fenômeno da imunotolerância na fotocarcinogênese em lábio.” 2011. Masters Thesis, University of São Paulo. Accessed January 16, 2021. http://www.teses.usp.br/teses/disponiveis/23/23141/tde-06032012-165809/ ;.

MLA Handbook (7^th Edition):

Dias, Renata Helena Ferreira Caramez Pierroni. “Análise do fenômeno da imunotolerância na fotocarcinogênese em lábio.” 2011. Web. 16 Jan 2021.

Vancouver:

Dias RHFCP. Análise do fenômeno da imunotolerância na fotocarcinogênese em lábio. [Internet] [Masters thesis]. University of São Paulo; 2011. [cited 2021 Jan 16]. Available from: http://www.teses.usp.br/teses/disponiveis/23/23141/tde-06032012-165809/ ;.

Council of Science Editors:

Dias RHFCP. Análise do fenômeno da imunotolerância na fotocarcinogênese em lábio. [Masters Thesis]. University of São Paulo; 2011. Available from: http://www.teses.usp.br/teses/disponiveis/23/23141/tde-06032012-165809/ ;

27. Endy Adnan. Cキナーゼ阻害剤で誘導されたヒト寛容型樹状細胞の抑制機能の解析 : 各種誘導寛容型樹状細胞との比較試験.

Degree: 博士(医学), 2016, Ehime University / 愛媛大学

URL: http://iyokan.lib.ehime-u.ac.jp/dspace/handle/iyokan/4973

博士(医学)

甲医博第831号

Subjects/Keywords: Immune tolerance; dendritic cells; regulatory T cells

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Adnan, E. (2016). Cキナーゼ阻害剤で誘導されたヒト寛容型樹状細胞の抑制機能の解析 : 各種誘導寛容型樹状細胞との比較試験. (Thesis). Ehime University / 愛媛大学. Retrieved from http://iyokan.lib.ehime-u.ac.jp/dspace/handle/iyokan/4973

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Adnan, Endy. “Cキナーゼ阻害剤で誘導されたヒト寛容型樹状細胞の抑制機能の解析 : 各種誘導寛容型樹状細胞との比較試験.” 2016. Thesis, Ehime University / 愛媛大学. Accessed January 16, 2021. http://iyokan.lib.ehime-u.ac.jp/dspace/handle/iyokan/4973.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Adnan, Endy. “Cキナーゼ阻害剤で誘導されたヒト寛容型樹状細胞の抑制機能の解析 : 各種誘導寛容型樹状細胞との比較試験.” 2016. Web. 16 Jan 2021.

Vancouver:

Adnan E. Cキナーゼ阻害剤で誘導されたヒト寛容型樹状細胞の抑制機能の解析 : 各種誘導寛容型樹状細胞との比較試験. [Internet] [Thesis]. Ehime University / 愛媛大学; 2016. [cited 2021 Jan 16]. Available from: http://iyokan.lib.ehime-u.ac.jp/dspace/handle/iyokan/4973.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Adnan E. Cキナーゼ阻害剤で誘導されたヒト寛容型樹状細胞の抑制機能の解析 : 各種誘導寛容型樹状細胞との比較試験. [Thesis]. Ehime University / 愛媛大学; 2016. Available from: http://iyokan.lib.ehime-u.ac.jp/dspace/handle/iyokan/4973

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

28. Danilo Mesquita Júnior. Avaliação fenotípica das células T reguladoras CD4+CD25+CD127LOW em pacientes com lúpus eritematoso sistêmico.

Degree: 2009, Universidade Federal de São Paulo

URL: http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=417 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=420 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=421 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=422 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=424 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=425 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=419

► O Lúpus Eritematoso Sistêmico (LES) é uma doença inflamatória crônica pertencente ao grupo das doenças reumáticas autoimunes sistêmicas, caracterizando- se por apresentar as mais variadas… (more)

▼ O Lúpus Eritematoso Sistêmico (LES) é uma doença inflamatória crônica pertencente ao grupo das doenças reumáticas autoimunes sistêmicas, caracterizando- se por apresentar as mais variadas manifestações clínicas e laboratoriais. Seu mecanismo exato de etiopatogenia ainda permanece obscuro. Observações prévias avaliando o papel das células TREG CD4+ CD25+ nas doenças autoimunes, em que se tem detectado tanto alterações de freqüência como alterações funcionas e fenotípicas em modelos murinos e humanos, sugerem o papel significante dessa população celular na etiopatogenia da autoimunidade. No LES podemos observar a existência de uma complexa rede de interações que caracterizam a doença, em que muitos alvos para intervenção terapêutica podem ser considerados. Atualmente tem-se voltado bastante a atenção para o estudo das células TREG CD4+CD25+, a fim de que possam ser usadas como alvos potenciais para terapia imunomoduladora. Os dados sobre a freqüência e fenótipo das células TREG publicados ate o momento são controversos devido à heterogeneidade de marcadores fenotípicos e estratégias de análises utilizadas. Um alto nível de células efetoras ativadas contaminam as amostras de células selecionadas de acordo com as estratégias clássicas de identificação de células TREG no LES e este fenômeno é ainda mais acentuado quanto maior o grau de atividade da doença. Assim, o presente projeto pretendeu inicialmente validar uma estratégia de análise capaz de identificar e quantificar células TREG utilizando a combinação dos marcadores CD25 e CD127 associados à expressão de Foxp3 em pacientes com LES em atividade ou fora de atividade. Concluiu-se pelo painel CD4+CD25+/highCD127Æ/low como melhor marcador de células TREG em virtude de sua alta associação com Foxp3 tanto em sadios como em pacientes com LES. Num segundo momento avaliamos a freqüência de células TREG e células Tconvonde observamos níveis normais de células TREG e níveis elevados de células Tconv ativadas em pacientes com doença em atividade. Foi nosso objetivo, também, avaliar a expressão de marcadores fenotípicos importantes para biologia das células TREG. Foi avaliada a expressão dos marcadores: CTLA-4, GITR, PD-1, OX40, HLA-DR, CD95, CD45Ra, CD28, CD40L nas células CD4+CD25+/hiCD127Æ/low, em pacientes com LES em fase ativa e inativa. Avaliamos também a relação entre o balanço de células TREG versus células Tconv expressando estes marcadores mediante o calculo da razão de equilíbrio fenotípico TREG/Tconv. Em pacientes com doença ativa observamos níveis diminuídos de células TREG positivas para as moléculas CTLA-4 e CD28 e níveis elevados de células TREG CD40L+. Quando avaliada a razão TREG/Tconv observamos uma alteração no balanço TREG/Tconv positivas para GITR, HLA-DR, OX40, CD40L e CD45RO. Houve queda na razão TREG/Tconv para os marcadores GITR, HLADR, OX40 e CD45RO e ganho para o marcador CD40L em pacientes com LES quando comparado a controles sadios. Além da caracterização fenotípica ampla, o presente estudo tem um ponto original extra, que consiste na definição da… Advisors/Committee Members: Luís Eduardo Coelho Andrade, Niels Olsen Saraiva Câmara, Esper Georges Kallás, Luiz Vicente Rizzo, Eloisa Silva Dutra de Oliveira Bonfa.

Subjects/Keywords: AUTO-IMUNIDADE; LUPUS ERITEMATOSO SISTEMICO; LINFOCITOS T; TOLERANCIA IMUNOLOGICA; CELULAS.; REUMATOLOGIA; TREG cells, Autoimmunity, LES, T lymphocytes, Immune tolerance

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Júnior, D. M. (2009). Avaliação fenotípica das células T reguladoras CD4+CD25+CD127LOW em pacientes com lúpus eritematoso sistêmico. (Thesis). Universidade Federal de São Paulo. Retrieved from http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=417 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=420 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=421 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=422 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=424 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=425 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=419

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Júnior, Danilo Mesquita. “Avaliação fenotípica das células T reguladoras CD4+CD25+CD127LOW em pacientes com lúpus eritematoso sistêmico.” 2009. Thesis, Universidade Federal de São Paulo. Accessed January 16, 2021. http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=417 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=420 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=421 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=422 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=424 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=425 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=419.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Júnior, Danilo Mesquita. “Avaliação fenotípica das células T reguladoras CD4+CD25+CD127LOW em pacientes com lúpus eritematoso sistêmico.” 2009. Web. 16 Jan 2021.

Vancouver:

Júnior DM. Avaliação fenotípica das células T reguladoras CD4+CD25+CD127LOW em pacientes com lúpus eritematoso sistêmico. [Internet] [Thesis]. Universidade Federal de São Paulo; 2009. [cited 2021 Jan 16]. Available from: http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=417 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=420 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=421 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=422 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=424 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=425 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=419.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Júnior DM. Avaliação fenotípica das células T reguladoras CD4+CD25+CD127LOW em pacientes com lúpus eritematoso sistêmico. [Thesis]. Universidade Federal de São Paulo; 2009. Available from: http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=417 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=420 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=421 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=422 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=424 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=425 ; http://www.bdtd.unifesp.br/tede//tde_busca/arquivo.php?codArquivo=419

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Queens University

29. Kot, Shalini. Induction of Immune Tolerance to Hexosaminidase M Using Rapamycin and Prednisone in the scAAV9-HEXM Gene Therapy Treatment of Sandhoff Disease .

Degree: Biomedical and Molecular Sciences, Queens University

URL: http://hdl.handle.net/1974/24862

► Sandhoff disease (SD) is a neurodegenerative disorder caused by the toxic accumulation of GM2 gangliosides in the brain. This is due to a deficient enzyme,… (more)

▼ Sandhoff disease (SD) is a neurodegenerative disorder caused by the toxic accumulation of GM2 gangliosides in the brain. This is due to a deficient enzyme, β-hexosaminidase A (HEXA), involved in the catabolism of GM2 gangliosides. A recently constructed isoenzyme analogous to HEXA, called Hexosaminidase M (HEXM), can efficiently catabolize GM2 gangliosides, while its gene can be compactly packaged into the self-complementary adeno-associated viral vector serotype 9 (scAAV9). Previous gene transfer studies have shown a significant survival benefit of scAAV9-HEXM in the hexb(-/-) knockout SD murine model. However, subsequent analyses revealed that scAAV9-HEXM has the potential to provoke an immune response against the expressed human HEXM product. This undesirable immune response can prove to be an obstacle for the long-term treatment efficacy, especially in individuals who lack the native HEXA protein (e.g., in infantile forms of the diseases). We hypothesized that suppressing the immune system will allow the body to tolerate the scAAV9-HEXM treatment and the newly-produced HEXM protein. Rapamycin (R) and prednisone (P) are immunosuppressants with a regulatory T-cell sparing effect, and both are used clinically to suppress cytotoxic immune responses. In this study, the administration of R and/or P in conjunction with scAAV9-HEXM was studied in SD mice. It was observed that administering both R and P long-term with scAAV9-HEXM demonstrated a significant reduction in antibody and IFN-g T cell responses to HEXM. which persisted after R&P administration ceased. This successful use of the R&P and scAAV9-HEXM resulted in significantly higher hexosaminidase enzyme activity levels in serum, reduced GM2 accumulation in the brain, and an increase in biodistribution of the vector in the liver. These mice also showed an extended lifespan beyond that achieved by the gene therapy in the absence of immunosuppression, with mice living for up to 7 weeks longer. The outcomes of this study may provide a proof-of-concept toleration immunosuppression regimen for long-term efficacy of not only the scAAV9-HEXM treatment, but also other gene therapy studies using AAV.

Subjects/Keywords: Gene Therapy ; Immune Tolerance ; Sandhoff Disease ; Rapamycin ; Prednisone

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kot, S. (n.d.). Induction of Immune Tolerance to Hexosaminidase M Using Rapamycin and Prednisone in the scAAV9-HEXM Gene Therapy Treatment of Sandhoff Disease . (Thesis). Queens University. Retrieved from http://hdl.handle.net/1974/24862

Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Kot, Shalini. “Induction of Immune Tolerance to Hexosaminidase M Using Rapamycin and Prednisone in the scAAV9-HEXM Gene Therapy Treatment of Sandhoff Disease .” Thesis, Queens University. Accessed January 16, 2021. http://hdl.handle.net/1974/24862.

Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Kot, Shalini. “Induction of Immune Tolerance to Hexosaminidase M Using Rapamycin and Prednisone in the scAAV9-HEXM Gene Therapy Treatment of Sandhoff Disease .” Web. 16 Jan 2021.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Vancouver:

Kot S. Induction of Immune Tolerance to Hexosaminidase M Using Rapamycin and Prednisone in the scAAV9-HEXM Gene Therapy Treatment of Sandhoff Disease . [Internet] [Thesis]. Queens University; [cited 2021 Jan 16]. Available from: http://hdl.handle.net/1974/24862.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.

Council of Science Editors:

Kot S. Induction of Immune Tolerance to Hexosaminidase M Using Rapamycin and Prednisone in the scAAV9-HEXM Gene Therapy Treatment of Sandhoff Disease . [Thesis]. Queens University; Available from: http://hdl.handle.net/1974/24862

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.

University of Vienna

30. Moroder, Susanne. Synthesis of indole derivatives as novel indoleamine 2,3-dioxygenase (IDO) inhibitors.

Degree: 2010, University of Vienna

URL: http://othes.univie.ac.at/8496/

►

Das immunsuppressive Enzym Indoleamine 2,3-dioxygenase, das eine Schlüsselfunktion im Tryptophan- Metabolismus einnimmt, wird seit geraumer Zeit mit Immuntoleranz gegenüber Tumorgewebe in Verbindung gebracht. Es wird… (more)

▼

Das immunsuppressive Enzym Indoleamine 2,3-dioxygenase, das eine Schlüsselfunktion im Tryptophan- Metabolismus einnimmt, wird seit geraumer Zeit mit Immuntoleranz gegenüber Tumorgewebe in Verbindung gebracht. Es wird in einigen Krebsarten überexprimiert und ist im Stande, durch lokalen Tryptophan-Abbau und die Akkumulierung der dadurch entstandenen cytotoxischen Metaboliten, die Proliferation der T-Zellen zu unterbinden und somit eine Immunantwort zu unterdrücken. Dieser Toleranzzustand verhindert zusätzlich eine erfolgreiche medikamentöse Therapie. Sowohl natürliche als auch synthetische Substanzen wurden als Hemmstoffe für das neu etablierte Zielmolekül entdeckt und entwickelt. Bisher wurden nur zwei davon direkt am Tumorgewebe getestet: 1-Methyl-tryptophan und Methyl-thiohydantoin-tryptophan. Tatsächlich zeigten beide in Kombination mit Paclitaxel eine signifikante Tumorregression. Das Ziel der vorliegenden Arbeit war es, neue Derivate von Methyl-thiohydantoin-tryptophan zu synthetisieren und sie sogleich auf ihre Enzym-Wirkung zu untersuchen. Die Syntheseprodukte zeigten jedoch eine geringere Inhibitionsaktivität am isolierten humanen IDO als ihre Muttersubstanz.

The immunomodulatory indoleamine 2,3-dioxygenase, a key enzyme of the tryptophan catabolism, is strongly connected to tumoural immune tolerance due to overexpression in certain tumours. Local depletion of the essential amino acid and the accumulation of cytotoxic tryptophan-derived metabolites induce an arrest of T-cell proliferation and suppress the immune response. This immune escaping state prevents an efficient immunotherapy as well. Natural just as synthetic compounds have been identified and developed for the novel drug target. Until now, only two of them have been assayed on tumour cells: 1-Methyl-tryptophan and Methyl-thiohydantoin-tryptophan. Both revealed, administered in combination with paclitaxel, a significant tumour regression. With the intent to develop novel small-molecule IDO inhibitors, we synthesized new derivatives based on Methyl-thiohydantoin-tryptophan scaffold. However, subsequently performed enzyme assay on human IDO displayed minor inhibitor activity as the parent substance.

Subjects/Keywords: 35.52 Präparative Organische Chemie; Indoleamine 2,3-dioxygenase / Immuntoleranz / Methyl-thiohydantoin-tryptophan; indoleamine 2,3-dioxygenase / tumoural immune tolerance / Methyl-thiohydantoin-tryptophan

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Moroder, S. (2010). Synthesis of indole derivatives as novel indoleamine 2,3-dioxygenase (IDO) inhibitors. (Thesis). University of Vienna. Retrieved from http://othes.univie.ac.at/8496/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Moroder, Susanne. “Synthesis of indole derivatives as novel indoleamine 2,3-dioxygenase (IDO) inhibitors.” 2010. Thesis, University of Vienna. Accessed January 16, 2021. http://othes.univie.ac.at/8496/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Moroder, Susanne. “Synthesis of indole derivatives as novel indoleamine 2,3-dioxygenase (IDO) inhibitors.” 2010. Web. 16 Jan 2021.

Vancouver:

Moroder S. Synthesis of indole derivatives as novel indoleamine 2,3-dioxygenase (IDO) inhibitors. [Internet] [Thesis]. University of Vienna; 2010. [cited 2021 Jan 16]. Available from: http://othes.univie.ac.at/8496/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Moroder S. Synthesis of indole derivatives as novel indoleamine 2,3-dioxygenase (IDO) inhibitors. [Thesis]. University of Vienna; 2010. Available from: http://othes.univie.ac.at/8496/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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