subject:(T cells)

1. Belmont, Judson. Technologies for Phosphoproteomic Interrogation of T Cell Signaling.

Degree: Department of Molecular Biology, Cell Biology and Biochemistry, 2017, Brown University

URL: https://repository.library.brown.edu/studio/item/bdr:792636/

► The ability to detect and adapt to changing conditions and circumstances is a requirement of life at both the organismal and cellular levels. Inside the… (more)

▼ The ability to detect and adapt to changing conditions and circumstances is a requirement of life at both the organismal and cellular levels. Inside the cell, rapid and fine-tuned responses to environmental cues can be achieved through dynamic post-translational modifications (PTMs) of proteins. Significant insights into the activity and dependencies of signaling pathways can therefore be gleaned from global surveys of PTM events, and in particular protein phosphorylation, as it is absolutely essential in the signaling cascades mediating the downstream functions of receptor tyrosine kinase systems. In T cells, coordinated phosphorylation of tyrosine residues is critical for transmission of signals from the activated T cell receptor. Investigations into the dynamic phosphoproteome of T cells have been greatly assisted by advances in mass spectrometry, which allows for the identification and quantitation of thousands of PTMs simultaneously without a requirement for site-specific antibodies. However, despite the increasing resolution and decreasing cost of mass spectrometry assays, the complex network of phosphorylation events governing T cell activation has been only incompletely characterized. In particular, while it is now appreciated that numerous feedback pathways within the T cell phosphoproteome work together to regulate the initiation of immune responses, when and where feedback loops occur in the pathway is poorly understood. To better understand the role that critical T cell signaling components play in feedback regulation of the T cell receptor pathway, we conducted a phosphoproteomic study into the role of Phospholipase C-γ1 in mediating the activation state of the receptor-proximal signaling machinery. Additionally, we investigated the application of optimized chromatography configurations to T cell phosphoproteomics, and demonstrated the immense potential to achieve greater qualitative and quantitative insights into the T cell signaling machinery. Finally, to support the visualization, management, annotation, and analysis of this proteomic data, we designed and implemented new tools to expedite discoveries from large LC-MS datasets. The subject of this work is therefore the insights we have gained into the mechanisms governing T cell activation and regulation as well as the technical and technological innovations that made those insights possible. Advisors/Committee Members: Salomon, Art (Advisor), Gruppuso, Philip (Reader), de Graffenreid, Christopher (Reader), Neretti, Nicola (Reader), Gerber, Scott (Reader).

Subjects/Keywords: T cells

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APA (6^th Edition):

Belmont, J. (2017). Technologies for Phosphoproteomic Interrogation of T Cell Signaling. (Thesis). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:792636/

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):

Belmont, Judson. “Technologies for Phosphoproteomic Interrogation of T Cell Signaling.” 2017. Thesis, Brown University. Accessed March 04, 2021. https://repository.library.brown.edu/studio/item/bdr:792636/.

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

MLA Handbook (7^th Edition):

Belmont, Judson. “Technologies for Phosphoproteomic Interrogation of T Cell Signaling.” 2017. Web. 04 Mar 2021.

Vancouver:

Belmont J. Technologies for Phosphoproteomic Interrogation of T Cell Signaling. [Internet] [Thesis]. Brown University; 2017. [cited 2021 Mar 04]. Available from: https://repository.library.brown.edu/studio/item/bdr:792636/.

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

Council of Science Editors:

Belmont J. Technologies for Phosphoproteomic Interrogation of T Cell Signaling. [Thesis]. Brown University; 2017. Available from: https://repository.library.brown.edu/studio/item/bdr:792636/

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

University of Oxford

2. Nguyen, John. Quantitative modelling of T cell activation and co-stimulation.

Degree: PhD, 2020, University of Oxford

URL: http://ora.ox.ac.uk/objects/uuid:2b713d2d-171c-4575-874c-6ad253a74484 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.808385

► Precisely regulated activity of T cells is crucial to effectively control pathogens while limiting immunopathology to a minimum. Even though T cell activation is predominantly… (more)

▼ Precisely regulated activity of T cells is crucial to effectively control pathogens while limiting immunopathology to a minimum. Even though T cell activation is predominantly governed by antigen recognition through the T cell receptor (TCR), the activity of an array of various accessory receptors can markedly alter this decision-making process, with the potential to serve as attractive therapeutic intervention points. Therefore, many of these co-stimulatory and co-inhibitory receptors and their molecular signalling pathways have been characterised. However, how exactly these receptors integrate with TCR signalling to affect the T cell response quantitatively remains poorly understood. Here, we used in vitro expanded primary human T cells in a minimal stimulation platform to study co-stimulation through receptors of the TNF receptor superfamily (TNFRSF) in isolation. This allowed us to precisely define the ligand doses and stimulation times in order to capture the quantitative effects of TNFRSF signalling on the T cell cytokine response, with a particular focus on two representative TNFRSF members, 4-1BB and CD27. We found that 4-1BB costimulation was able to prolong the cytokine response, while engagement of CD27 increased the amount of cytokine produced without affecting the duration of the response and the T cells still became unresponsive after 8 hours. However, in combination with computational modelling, detailed analysis of our results showed that the distinct phenotypes of these receptors were mainly caused by their differential expression pattern in time, while the TNFRSF members share a common co-stimulatory mechanism, which we summarised in a minimal mathematical model. Simulations of the model predicted that co-stimulation through either of 4-1BB and CD27 could rescue TCR-dependent cytokine production in T cells which had become unresponsive through previous stimulation, and that CD27 could increase the potency of 4-1BB by enhancing its expression. We were then able to validate the model by confirming the both the rescue of the response and the synergy between TNFRSF members experimentally.

Subjects/Keywords: immunology; T cells

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APA (6^th Edition):

Nguyen, J. (2020). Quantitative modelling of T cell activation and co-stimulation. (Doctoral Dissertation). University of Oxford. Retrieved from http://ora.ox.ac.uk/objects/uuid:2b713d2d-171c-4575-874c-6ad253a74484 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.808385

Chicago Manual of Style (16^th Edition):

Nguyen, John. “Quantitative modelling of T cell activation and co-stimulation.” 2020. Doctoral Dissertation, University of Oxford. Accessed March 04, 2021. http://ora.ox.ac.uk/objects/uuid:2b713d2d-171c-4575-874c-6ad253a74484 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.808385.

MLA Handbook (7^th Edition):

Nguyen, John. “Quantitative modelling of T cell activation and co-stimulation.” 2020. Web. 04 Mar 2021.

Vancouver:

Nguyen J. Quantitative modelling of T cell activation and co-stimulation. [Internet] [Doctoral dissertation]. University of Oxford; 2020. [cited 2021 Mar 04]. Available from: http://ora.ox.ac.uk/objects/uuid:2b713d2d-171c-4575-874c-6ad253a74484 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.808385.

Council of Science Editors:

Nguyen J. Quantitative modelling of T cell activation and co-stimulation. [Doctoral Dissertation]. University of Oxford; 2020. Available from: http://ora.ox.ac.uk/objects/uuid:2b713d2d-171c-4575-874c-6ad253a74484 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.808385

3. Nevers, Tania A. Inflammatory and dysfunctional regulatory T cells in adverse pregnancy outcomes.

Degree: PhD, Pathobiology, 2012, Brown University

URL: https://repository.library.brown.edu/studio/item/bdr:297562/

► The etiologies for adverse pregnancy outcomes such as recurrent spontaneous abortion, preeclampsia, preterm birth and gestational diabetes mellitus (GDM) are multi-factorial and remain poorly understood.… (more)

▼ The etiologies for adverse pregnancy outcomes such as recurrent spontaneous abortion, preeclampsia, preterm birth and gestational diabetes mellitus (GDM) are multi-factorial and remain poorly understood. The main reasons for enigmatic state of adverse pregnancy outcomes can be assigned to lack of well defined animal models in response to inflammatory triggers and early pregnancy predictive assays and biomarkers. However, these pregnancy complications have a common contributor in inflammation at the maternal-fetal interface. In normal pregnancy, a state of immune tolerance is choreographed involving pro- and anti-inflammatory signals. Regulatory T cells (Tregs) have acquired a premier role in regulating immune tolerance systemically and at the maternal-fetal interface. Here we focus on Tregs for their phenotypic and functional dysregulation in mouse and human models of pregnancy complications. Importantly, we invoke the role of IL-10, a signature cytokine of Tregs, and human chorionic gonadotropin (hCG) in maintaining normal pregnancy. Our overarching hypothesis is that uterine regulatory T cells are dysfunctional in adverse pregnancies associated with infection and /or inflammation and may be normalized by IL-10 and hCG. This work explores dysregulation of uterine Tregs by utilizing mouse models of adverse pregnancies, human peripheral blood Tregs and sera from normal pregnancy, preeclampsia and gestational diabetes. In Chapter 2, we show that uterine regulatory T cells amplify and acquire an inflammatory phenotype in response to the TLR-3 agonist and cause pregnancy demise in IL-10-/- and wild-type (WT) mice. In Chapter 3, we present for the first time that peripheral blood Tregs from GDM patients present an “exhausted” phenotype and express the programmed death receptor (PD-1). Tregs from GDM lose CD25 and Foxp3 expression upon overnight culturing which can be partially rescued by TGF-β, IL-2, or PD-1 blockade. This phenotype was not observed in Tregs from normal pregnancy. In Chapter 4, we describe that hCG produced in preeclampsia is inactive and does not support angiogenesis and recruitment of Tregs to the uterus in the “humanized” mouse model of preeclampsia. Collectively, the results presented in this thesis provide novel pathways by which regulatory T cells can present themselves as foes of normal pregnancy. Advisors/Committee Members: Sharma, Surendra (Director), Ayala, alfred (Reader), Fast, Loren (Reader), Reichner, Jonathan (Reader), Golos, Thaddeus (Reader).

Subjects/Keywords: Regulatory T cells

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APA (6^th Edition):

Nevers, T. A. (2012). Inflammatory and dysfunctional regulatory T cells in adverse pregnancy outcomes. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:297562/

Chicago Manual of Style (16^th Edition):

Nevers, Tania A. “Inflammatory and dysfunctional regulatory T cells in adverse pregnancy outcomes.” 2012. Doctoral Dissertation, Brown University. Accessed March 04, 2021. https://repository.library.brown.edu/studio/item/bdr:297562/.

MLA Handbook (7^th Edition):

Nevers, Tania A. “Inflammatory and dysfunctional regulatory T cells in adverse pregnancy outcomes.” 2012. Web. 04 Mar 2021.

Vancouver:

Nevers TA. Inflammatory and dysfunctional regulatory T cells in adverse pregnancy outcomes. [Internet] [Doctoral dissertation]. Brown University; 2012. [cited 2021 Mar 04]. Available from: https://repository.library.brown.edu/studio/item/bdr:297562/.

Council of Science Editors:

Nevers TA. Inflammatory and dysfunctional regulatory T cells in adverse pregnancy outcomes. [Doctoral Dissertation]. Brown University; 2012. Available from: https://repository.library.brown.edu/studio/item/bdr:297562/

4. Ruiz, Victoria E. Immune response to Helicobacter pylori infection in the gastric cancer prone p27-deficient mouse model.

Degree: PhD, Pathobiology, 2012, Brown University

URL: https://repository.library.brown.edu/studio/item/bdr:297572/

► Helicobacter pylori infection is associated with severe chronic inflammation, however the host immune response is unable to clear the bacterium. Thymus derived lymphocyte populations such… (more)

▼ Helicobacter pylori infection is associated with severe chronic inflammation, however the host immune response is unable to clear the bacterium. Thymus derived lymphocyte populations such as T-helper 1, T-helper 17, and T-regulatory lymphocytes are known to promote chronicity of infection as well as increased gastric pathology. It is yet to be established how these immune cells interact in the gastric environment during H. pylori infection and how changes in the gastric T- lymphocyte cell repertoire may lead gastric cancer associated pathology. To first characterize gastric T-lymphocyte populations, a gastric lymphocyte isolation technique was developed. H. pylori infected murine gastric tissue was digested with EDTA/DTT and collagenase IV. To enrich for gastric lymphocyte populations, a lympholyte M gradient was used. This protocol successfully isolated 1x 106 viable lymphocytes from the gastric compartment to be used for ex vivo experiments and subsequent immunophenotyping using flow cytometric analysis. Using this procedure a 2-fold increase of CD8+ IFNg-expressing lymphocytes was observed in the gastric compartment during H. pylori infection. Implementing the established gastric lymphocyte isolation technique, gastric T-helper and T-regulatory lymphocyte populations were evaluated in p27-deficient mice. These mice develop gastric cancer a year after H. pylori infection, mimicking the human clinical course of disease. Thus providing a suitable model to study H. pylori induced immunopathogenesis. This work demonstrated that H. pylori infected p27-deficient mice displayed an increased frequency of CD4+ IFNγ+ T helper populations in the stomach, spleen and mesenteric lymph nodes. Additionally, infected p27-deficient mice exhibited elevated protein and transcript levels of pro-inflammatory cytokines IFNγ, TNFα, ΙL-12p40 and chemokine, RANTES. Along with a significant Th-1 skewed response, p27-deficient mice exhibited decreased H. pylori colonization and increased gastric pathology compared to its wild-type counterparts. This data demonstrates that in p27-deficient mice, H. pylori induces a pro-inflammatory environment by recruiting Th1 cells to the gastric mucosa and other lymphoid compartments. Data suggest that this recruitment, likely mediated by RANTES, may contribute to subsequent gastric pathogenesis and eventual bacterial clearance. Advisors/Committee Members: Moss, Steven (Director), Ayala, Alfred (Reader), Fast, Loren (Reader), Salazar-Mather, Thais (Reader), Perez-Perez, Guillermo (Reader).

Subjects/Keywords: T-helper cells

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APA (6^th Edition):

Ruiz, V. E. (2012). Immune response to Helicobacter pylori infection in the gastric cancer prone p27-deficient mouse model. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:297572/

Chicago Manual of Style (16^th Edition):

Ruiz, Victoria E. “Immune response to Helicobacter pylori infection in the gastric cancer prone p27-deficient mouse model.” 2012. Doctoral Dissertation, Brown University. Accessed March 04, 2021. https://repository.library.brown.edu/studio/item/bdr:297572/.

MLA Handbook (7^th Edition):

Ruiz, Victoria E. “Immune response to Helicobacter pylori infection in the gastric cancer prone p27-deficient mouse model.” 2012. Web. 04 Mar 2021.

Vancouver:

Ruiz VE. Immune response to Helicobacter pylori infection in the gastric cancer prone p27-deficient mouse model. [Internet] [Doctoral dissertation]. Brown University; 2012. [cited 2021 Mar 04]. Available from: https://repository.library.brown.edu/studio/item/bdr:297572/.

Council of Science Editors:

Ruiz VE. Immune response to Helicobacter pylori infection in the gastric cancer prone p27-deficient mouse model. [Doctoral Dissertation]. Brown University; 2012. Available from: https://repository.library.brown.edu/studio/item/bdr:297572/

University of Oxford

5. Kurioka, Ayako. Mucosal associated invariant T cells and CD161 expressing natural killer cells.

Degree: PhD, 2015, University of Oxford

URL: https://ora.ox.ac.uk/objects/uuid:f994e661-d241-4a1c-ac56-b6bea73346ac ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.730591

► Mucosal-associated invariant T (MAIT) cells are a population of innate-like lymphocytes within the gut, liver and blood, expressing a semi-invariant T cell receptor (TCR) and… (more)

Subjects/Keywords: 616.07; T cells

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APA (6^th Edition):

Kurioka, A. (2015). Mucosal associated invariant T cells and CD161 expressing natural killer cells. (Doctoral Dissertation). University of Oxford. Retrieved from https://ora.ox.ac.uk/objects/uuid:f994e661-d241-4a1c-ac56-b6bea73346ac ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.730591

Chicago Manual of Style (16^th Edition):

Kurioka, Ayako. “Mucosal associated invariant T cells and CD161 expressing natural killer cells.” 2015. Doctoral Dissertation, University of Oxford. Accessed March 04, 2021. https://ora.ox.ac.uk/objects/uuid:f994e661-d241-4a1c-ac56-b6bea73346ac ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.730591.

MLA Handbook (7^th Edition):

Kurioka, Ayako. “Mucosal associated invariant T cells and CD161 expressing natural killer cells.” 2015. Web. 04 Mar 2021.

Vancouver:

Kurioka A. Mucosal associated invariant T cells and CD161 expressing natural killer cells. [Internet] [Doctoral dissertation]. University of Oxford; 2015. [cited 2021 Mar 04]. Available from: https://ora.ox.ac.uk/objects/uuid:f994e661-d241-4a1c-ac56-b6bea73346ac ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.730591.

Council of Science Editors:

Kurioka A. Mucosal associated invariant T cells and CD161 expressing natural killer cells. [Doctoral Dissertation]. University of Oxford; 2015. Available from: https://ora.ox.ac.uk/objects/uuid:f994e661-d241-4a1c-ac56-b6bea73346ac ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.730591

University of Gothenburg / Göteborgs Universitet

6. Alsén, Samuel. Dendritic cells and B cells in effector T cells decisions - promotion of antibody induction in lymphoid tissues or gut homing.

Degree: 2018, University of Gothenburg / Göteborgs Universitet

URL: http://hdl.handle.net/2077/55393

► Abstract CD4+ T cells are principal cells of the adaptive immune system, equipped with the ability to boost innate immune cells and aid B cells… (more)

Subjects/Keywords: Immunology; T cells; T follicular helper cells; dendritic cells

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APA (6^th Edition):

Alsén, S. (2018). Dendritic cells and B cells in effector T cells decisions - promotion of antibody induction in lymphoid tissues or gut homing. (Thesis). University of Gothenburg / Göteborgs Universitet. Retrieved from http://hdl.handle.net/2077/55393

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):

Alsén, Samuel. “Dendritic cells and B cells in effector T cells decisions - promotion of antibody induction in lymphoid tissues or gut homing.” 2018. Thesis, University of Gothenburg / Göteborgs Universitet. Accessed March 04, 2021. http://hdl.handle.net/2077/55393.

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

MLA Handbook (7^th Edition):

Alsén, Samuel. “Dendritic cells and B cells in effector T cells decisions - promotion of antibody induction in lymphoid tissues or gut homing.” 2018. Web. 04 Mar 2021.

Vancouver:

Alsén S. Dendritic cells and B cells in effector T cells decisions - promotion of antibody induction in lymphoid tissues or gut homing. [Internet] [Thesis]. University of Gothenburg / Göteborgs Universitet; 2018. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/2077/55393.

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

Council of Science Editors:

Alsén S. Dendritic cells and B cells in effector T cells decisions - promotion of antibody induction in lymphoid tissues or gut homing. [Thesis]. University of Gothenburg / Göteborgs Universitet; 2018. Available from: http://hdl.handle.net/2077/55393

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

Queen Mary, University of London

7. Kishore, Madhav. The role of co-stimulatory receptors in the regulation of regulatory T cell migration.

Degree: PhD, 2016, Queen Mary, University of London

URL: http://qmro.qmul.ac.uk/xmlui/handle/123456789/12869 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775244

► Once an immune response is initiated, a combination of several mechanisms coordinates and directs the homing of T cells to their target tissue. Co-stimulatory receptors… (more)

▼ Once an immune response is initiated, a combination of several mechanisms coordinates and directs the homing of T cells to their target tissue. Co-stimulatory receptors expressed on the surface of T lymphocytes are known to actively regulate T cell motility and thus are crucial for regulating T cell migration. The B7 co-stimulatory receptor family members CD28 and CTLA-4 are well known to positively and negatively regulate effector T cell motility respectively. However, their effect on motility and subsequently migration has not been specifically studied in regulatory T cells (Tregs). Tregs are a CD4+ T cell subset fundamental for maintaining immune homeostasis and their role in controlling autoimmunity has been well established through a variety of experimental animal models. Tregs differ from conventional T cells in their expression of CTLA-4. While conventional T cells express CTLA-4 only after activation, Tregs are known to express this negative co-stimulatory receptor constitutively. Additionally, Tregs display a distinct metabolic phenotype to that of conventional T cells. This thesis examines the impact of both co-stimulatory receptors on Treg migration while taking in account the consequences of the concomitant delivery of signals from both. The data in this study suggests that glycolysis, rather than lipid oxidation induced by CD28 promotes Treg migration through glycolytic enzymes including glucokinase, whose expression in T cells was previously unknown. In contrast, CTLA-4 inhibits CD28 induced Treg migration via inhibition of these glycolytic enzymes. The therapeutic implications of these results in the context of disease and transplantation are discussed. CD31, an IgG like molecule, is expressed on a number of leukocytes including lymphocytes. In T cells, CD31 inhibits activation by recruiting phosphatases through its cytoplasmic ITIM domains and has thus been described as a co-inhibitory receptor. The role of this co-receptor in the regulation of T cell migration is investigated in the last part of this thesis. Our observations suggest that CD31 selectively signals in activated T cells to regulate their migration in response to inflammatory chemokines, revealing an additional role of this receptor in regulating T cell-mediated inflammation.

Subjects/Keywords: Medicine; regulatory T cells; T cell migration

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APA (6^th Edition):

Kishore, M. (2016). The role of co-stimulatory receptors in the regulation of regulatory T cell migration. (Doctoral Dissertation). Queen Mary, University of London. Retrieved from http://qmro.qmul.ac.uk/xmlui/handle/123456789/12869 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775244

Chicago Manual of Style (16^th Edition):

Kishore, Madhav. “The role of co-stimulatory receptors in the regulation of regulatory T cell migration.” 2016. Doctoral Dissertation, Queen Mary, University of London. Accessed March 04, 2021. http://qmro.qmul.ac.uk/xmlui/handle/123456789/12869 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775244.

MLA Handbook (7^th Edition):

Kishore, Madhav. “The role of co-stimulatory receptors in the regulation of regulatory T cell migration.” 2016. Web. 04 Mar 2021.

Vancouver:

Kishore M. The role of co-stimulatory receptors in the regulation of regulatory T cell migration. [Internet] [Doctoral dissertation]. Queen Mary, University of London; 2016. [cited 2021 Mar 04]. Available from: http://qmro.qmul.ac.uk/xmlui/handle/123456789/12869 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775244.

Council of Science Editors:

Kishore M. The role of co-stimulatory receptors in the regulation of regulatory T cell migration. [Doctoral Dissertation]. Queen Mary, University of London; 2016. Available from: http://qmro.qmul.ac.uk/xmlui/handle/123456789/12869 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775244

University of Manchester

8. Dookie, Rebecca. Dissecting the molecular mechanisms of CD4+ T cell exhaustion during malaria.

Degree: 2019, University of Manchester

URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:319548

►

Malaria is a global life-threatening disease responsible for 400,000 deaths each year. Chronic infection with Plasmodium species drives CD4+ T cell exhaustion, which is characterised… (more)

▼

Malaria is a global life-threatening disease responsible for 400,000 deaths each year. Chronic infection with Plasmodium species drives CD4+ T cell exhaustion, which is characterised by the inability of effector CD4+ T cells to produce effector cytokines, proliferate and increased T cell apoptosis. T cell exhaustion significantly impairs parasite control during blood stage malaria. However, the molecular mechanisms promoting CD4+ T cell exhaustion during malaria are poorly understood. Using a model antigen-specific CD4+ T cell system, we have shown that effector CD4+ T cells rapidly become functionally exhausted during P.yoelii infection. The degradation of the effector CD4+ T cell response appeared to relate to the loss of MHC II-TCR signalling, as blockade of MHC II signalling, post priming, did not exacerbate effector T cell dysfunction and attrition during malaria. However, apparent loss of MHC II activation during infection was not due to alterations in CD4+ T cell compartmentalisation, or inability of effector CD4+ T cells to interact with antigen presenting cells (APC) during infection. Instead, we propose that negative signals from co-inhibitory receptors subvert peptide MHC II-TCR signals in effector CD4+ T cells, contributing to T cell exhaustion during blood stage malaria. To further investigate the role of co-inhibitory receptors in promoting CD4+ T cell exhaustion during malaria, we administered antagonistic antibodies against TIGIT and PD-L1. Dual blockade of TIGIT and PD-L1 significantly enhanced parasite control, which correlated with an increased level of systemic interferon gamma (IFNg) and an enhanced T follicular helper response during infection. Surprisingly, however, dual blockade of TIGIT and PD-L1 did not significantly improve effector CD4+ T cell function. Thus, blockade of TIGIT and PD-1 signalling pathways cannot prevent CD4+ T cell exhaustion during malaria. We also investigated the synergistic role of Tim3 and PD-1 in promoting CD4+ T cell exhaustion during malaria. Interestingly, Tim3 was transiently expressed on effector CD4+ T cells and was downregulated as T cell exhaustion was established during infection. In agreement, co-blockade of Tim3 and PD-L1 failed to improve CD4+ T cell functionality during P.yoelii infection, suggesting that Tim3 does not contribute to CD4+ T cell exhaustion during malaria. Collectively, this thesis has shown that effector CD4+ T cell exhaustion is not associated with the inability of T cells to form stable interactions with APC during infection, but instead we propose that multiple immunoregulatory pathways act in parallel to orchestrate T cell exhaustion during blood stage malaria.

USB containing supplementary movies submitted in a pocket on the inside back cover of the printed version of thesis.

Advisors/Committee Members: MACDONALD, ANDREW AS, Couper, Kevin, Macdonald, Andrew.

Subjects/Keywords: CD4+ T cells; Malaria; T cell exhaustion

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APA (6^th Edition):

Dookie, R. (2019). Dissecting the molecular mechanisms of CD4+ T cell exhaustion during malaria. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:319548

Chicago Manual of Style (16^th Edition):

Dookie, Rebecca. “Dissecting the molecular mechanisms of CD4+ T cell exhaustion during malaria.” 2019. Doctoral Dissertation, University of Manchester. Accessed March 04, 2021. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:319548.

MLA Handbook (7^th Edition):

Dookie, Rebecca. “Dissecting the molecular mechanisms of CD4+ T cell exhaustion during malaria.” 2019. Web. 04 Mar 2021.

Vancouver:

Dookie R. Dissecting the molecular mechanisms of CD4+ T cell exhaustion during malaria. [Internet] [Doctoral dissertation]. University of Manchester; 2019. [cited 2021 Mar 04]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:319548.

Council of Science Editors:

Dookie R. Dissecting the molecular mechanisms of CD4+ T cell exhaustion during malaria. [Doctoral Dissertation]. University of Manchester; 2019. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:319548

Universiteit Utrecht

9. Munting, L.P. Reviewing seasonal child vaccination against influenza: An evaluation of the pros and cons.

Degree: 2015, Universiteit Utrecht

URL: http://dspace.library.uu.nl:8080/handle/1874/303162

► Influenza is an infectious, respiratory disease, which may cause symptoms in healthy individuals for several weeks. Serious complications or death may occur in the elderly… (more)

Subjects/Keywords: influenza; child vaccination; T cells

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APA (6^th Edition):

Munting, L. P. (2015). Reviewing seasonal child vaccination against influenza: An evaluation of the pros and cons. (Masters Thesis). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/303162

Chicago Manual of Style (16^th Edition):

Munting, L P. “Reviewing seasonal child vaccination against influenza: An evaluation of the pros and cons.” 2015. Masters Thesis, Universiteit Utrecht. Accessed March 04, 2021. http://dspace.library.uu.nl:8080/handle/1874/303162.

MLA Handbook (7^th Edition):

Munting, L P. “Reviewing seasonal child vaccination against influenza: An evaluation of the pros and cons.” 2015. Web. 04 Mar 2021.

Vancouver:

Munting LP. Reviewing seasonal child vaccination against influenza: An evaluation of the pros and cons. [Internet] [Masters thesis]. Universiteit Utrecht; 2015. [cited 2021 Mar 04]. Available from: http://dspace.library.uu.nl:8080/handle/1874/303162.

Council of Science Editors:

Munting LP. Reviewing seasonal child vaccination against influenza: An evaluation of the pros and cons. [Masters Thesis]. Universiteit Utrecht; 2015. Available from: http://dspace.library.uu.nl:8080/handle/1874/303162

Tulane University

10. Moss, Daniel. Antigen Stability Influences Processing Efficiency and Immunogenicity of Pseudomonas Exotoxin Domain III and Ovalbumin.

Degree: 2020, Tulane University

URL: https://digitallibrary.tulane.edu/islandora/object/tulane:120437

►

[email protected]

Effective adaptive immune responses depend on the presentation to CD4+ T cells antigen peptides bound to major histocompatibility complex class II proteins. The structure… (more)

▼

[email protected]

Effective adaptive immune responses depend on the presentation to CD4+ T cells antigen peptides bound to major histocompatibility complex class II proteins. The structure of an antigen strongly influences its processing within the endolysosome and potentially controls the identity and abundance of peptides that are presented to T cells. The dissertation presented here sought to expand our understanding of how antigen structure and stability influence adaptive immune responses for two model antigens. Pseudomonas exotoxin A domain III (PE-III) functions as an ADP-ribosyltransferase with significant cellular toxicity and has been incorporated into a recombinant immunotoxin for the treatment of cancer. The bacterial component of the PE-III immunotoxin is highly immunogenic and generates neutralizing antibodies that render subsequent treatments ineffective. A group of six single-amino-acid substitutions in PE-III that were predicted to disrupt CD4+ T-cell epitopes have been shown to reduce antibody responses in mice. Here we demonstrate that only one of the substitutions, R494A, exhibits reduced folding stability and proteolytic resistance through the removal of a hydrogen bond. This destabilization significantly reduces its antibody immunogenicity while generating CD4+ T-cell epitopes that are indistinguishable from those of wildtype PE-III. PE-III specific B cells isolated from R494A-immunized animals contained fewer somatic mutations, which are associated with affinity maturation, and exhibited a weaker germinal-center gene signature, compared to B cells from wildtype-immunized animals. Chicken ovalbumin (cOVA) has been studied for decades primarily due to the robust genetic and molecular resources that are available for experimental investigations. cOVA is a member of the serpin superfamily of proteins that function as protease inhibitors, although cOVA does not exhibit this activity. As a serpin, cOVA possess a protease-sensitive reactive center loop that lies adjacent to the OT-II epitope. We took advantage of the previously described single-substitution-variant, OVA R339T, which can undergo the dramatic structural transition observed in serpins to study how changes in loop size and protein stability influences CD4+ T-cell priming in vivo. We observed that OVA R339T loop-insertion increases overall stability and protease resistance and significantly shortens the reactive center loop. This results in reduced CD4+ T-cell priming of the OT-II epitope in SJL mice. These findings have implications for the design of more effective vaccines for the treatment of infectious diseases and cancer as well as the development of more robust CD4+ T-cell epitope prediction tools.

1

Daniel Moss

Advisors/Committee Members: Landry, Samuel (Thesis advisor), School of Medicine Biomedical Sciences Graduate Program (Degree granting institution).

Subjects/Keywords: CD4+ T cells Antigen Processing

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

APA (6^th Edition):

Moss, D. (2020). Antigen Stability Influences Processing Efficiency and Immunogenicity of Pseudomonas Exotoxin Domain III and Ovalbumin. (Thesis). Tulane University. Retrieved from https://digitallibrary.tulane.edu/islandora/object/tulane:120437

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):

Moss, Daniel. “Antigen Stability Influences Processing Efficiency and Immunogenicity of Pseudomonas Exotoxin Domain III and Ovalbumin.” 2020. Thesis, Tulane University. Accessed March 04, 2021. https://digitallibrary.tulane.edu/islandora/object/tulane:120437.

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

MLA Handbook (7^th Edition):

Moss, Daniel. “Antigen Stability Influences Processing Efficiency and Immunogenicity of Pseudomonas Exotoxin Domain III and Ovalbumin.” 2020. Web. 04 Mar 2021.

Vancouver:

Moss D. Antigen Stability Influences Processing Efficiency and Immunogenicity of Pseudomonas Exotoxin Domain III and Ovalbumin. [Internet] [Thesis]. Tulane University; 2020. [cited 2021 Mar 04]. Available from: https://digitallibrary.tulane.edu/islandora/object/tulane:120437.

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

Council of Science Editors:

Moss D. Antigen Stability Influences Processing Efficiency and Immunogenicity of Pseudomonas Exotoxin Domain III and Ovalbumin. [Thesis]. Tulane University; 2020. Available from: https://digitallibrary.tulane.edu/islandora/object/tulane:120437

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

University of Alberta

11. Hockley, Deanna L. Co-stimulator contributions in CD8+ T cell differentiation.

Degree: PhD, Department of Medical Microbiology and Immunology, 2012, University of Alberta

URL: https://era.library.ualberta.ca/files/f4752h04p

► The adaptive immune response against intracellular pathogens is largely mediated by CD8+ T lymphocytes. The clonal expansion and expression of cytolytic and immune stimulatory proteins… (more)

▼ The adaptive immune response against intracellular pathogens is largely mediated by CD8+ T lymphocytes. The clonal expansion and expression of cytolytic and immune stimulatory proteins by CD8+ T cells is responsible for their protective immune function. Prior to exhibiting effector activity, CD8+ T cells exist in a naïve state and require three stimulatory signals for their optimal activation including the recognition of antigen, co-stimulator ligand engagement, and the presence of pro-inflammatory cytokines. When these activation requirements are met, CD8+ T cells undergo a well described series of events including clonal expansion, cellular contraction, memory generation, and memory maintenance. The memory CD8+ T cell population generated can survive for the life-time of the host, and provides more rapid and robust protection upon re-infection then their naïve precursors. While some factors that induce this sequence of events have been identified, the role of co-stimulation remains relatively undefined. This is due to the large number of co-stimulator receptors expressed by CD8+ T cells that may be ligated individually and/or in combination, to instruct the development of specific effector and memory CD8+ T cell phenotypes. Using a bead-based ligand presentation system, I investigated the role of co-stimulation in directing naïve CD8+ T cell activation, and the generation of T cell populations with distinct effector and memory fates. I identified ICAM-1 as the stimulatory molecule best able to induce naïve CD8+ T cell proliferation and expression of the effector molecule granzyme B, while co-stimulation through CD28 was required to induce IFN-γ. When provided in combination however, B7.1 and ICAM-1 co-stimulation generated CD8+ T cells which were highly cytolytic and expressed high amounts of IFN-γ. These cells also exhibited enhanced survival once activated, with sustained expression of anti-apoptotic proteins and secretion of high amounts of IL-2, resulting in these cells exhibiting a terminal effector phenotype. While other co-stimulator combinations also enhanced CD8+ T cell survival to some degree, their ability to sustain high expression of IL-2 was limited. This translated into less potent effector responses and preferential memory precursor development based on transcription factor expression.

Subjects/Keywords: Immunology; T cells; Co-stimulation

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

APA (6^th Edition):

Hockley, D. L. (2012). Co-stimulator contributions in CD8+ T cell differentiation. (Doctoral Dissertation). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/f4752h04p

Chicago Manual of Style (16^th Edition):

Hockley, Deanna L. “Co-stimulator contributions in CD8+ T cell differentiation.” 2012. Doctoral Dissertation, University of Alberta. Accessed March 04, 2021. https://era.library.ualberta.ca/files/f4752h04p.

MLA Handbook (7^th Edition):

Hockley, Deanna L. “Co-stimulator contributions in CD8+ T cell differentiation.” 2012. Web. 04 Mar 2021.

Vancouver:

Hockley DL. Co-stimulator contributions in CD8+ T cell differentiation. [Internet] [Doctoral dissertation]. University of Alberta; 2012. [cited 2021 Mar 04]. Available from: https://era.library.ualberta.ca/files/f4752h04p.

Council of Science Editors:

Hockley DL. Co-stimulator contributions in CD8+ T cell differentiation. [Doctoral Dissertation]. University of Alberta; 2012. Available from: https://era.library.ualberta.ca/files/f4752h04p

University of Alberta

12. He, Jinshu. Regulation of FasL expression and trafficking in cytotoxic T lymphocytes.

Degree: PhD, Department of Medical Microbiology and Immunology, 2009, University of Alberta

URL: https://era.library.ualberta.ca/files/4x51hj17q

► Cytotoxic T lymphocytes (CTL) are differentiated CD8+ T cells that eliminate virally infected cells and tumor cells. CTL lyse target cells by at least two… (more)

Subjects/Keywords: cytotoxicity; T cells; Fas ligand

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

APA (6^th Edition):

He, J. (2009). Regulation of FasL expression and trafficking in cytotoxic T lymphocytes. (Doctoral Dissertation). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/4x51hj17q

Chicago Manual of Style (16^th Edition):

He, Jinshu. “Regulation of FasL expression and trafficking in cytotoxic T lymphocytes.” 2009. Doctoral Dissertation, University of Alberta. Accessed March 04, 2021. https://era.library.ualberta.ca/files/4x51hj17q.

MLA Handbook (7^th Edition):

He, Jinshu. “Regulation of FasL expression and trafficking in cytotoxic T lymphocytes.” 2009. Web. 04 Mar 2021.

Vancouver:

He J. Regulation of FasL expression and trafficking in cytotoxic T lymphocytes. [Internet] [Doctoral dissertation]. University of Alberta; 2009. [cited 2021 Mar 04]. Available from: https://era.library.ualberta.ca/files/4x51hj17q.

Council of Science Editors:

He J. Regulation of FasL expression and trafficking in cytotoxic T lymphocytes. [Doctoral Dissertation]. University of Alberta; 2009. Available from: https://era.library.ualberta.ca/files/4x51hj17q

13. 佐伯, 晃一. THEORETICAL STUDIES OF SELF-TOLERANCE : REGULATORY T CELLS AND ANERGY : 自己寛容に関する理論的研究 : 制御性Ｔ細胞とアナジーについて.

Degree: 博士（理学）, 2013, Kyushu University / 九州大学

URL: http://hdl.handle.net/2324/21712 ; http://dx.doi.org/10.15017/21712

自己寛容とは免疫システムが自分の体に対して反応を示さない状態のことである。これは生物が生まれながらに持っている性質ではなく、成立にはその為のメカニズムが必要である。例えば、獲得免疫系を担うリンパ球はランダムに生成された受容体を用いて抗原の認識を行うため、自分の体由来の抗原を認識するリンパ球も作られる。そのため成熟前に受容体をチェックし、自己抗原を認識するものは排除する(負の選択)機構が存在する。しかしながら、このチェック機構だけでは不十分であり、リンパ球の成熟後に末梢において自己寛容を保証するメカニズムがあることが知られている。自己寛容の破綻は自己免疫疾患につながるため、メカニズムの理解は医学的な観点からも注目を集めている。本論文では、自己寛容の成立に関わっている二つの機構、制御性T細胞とアナジーに着目しそれらの意義ついて数理モデルを用いて議論した。二つの機構は常に有益となるわけではなく、幾つかの条件下で有利に働くことが分かった。 Advisors/Committee Members: 巌佐, 庸.

Subjects/Keywords: self-tolerance; regulatory T cells

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APA (6^th Edition):

佐伯, �. (2013). THEORETICAL STUDIES OF SELF-TOLERANCE : REGULATORY T CELLS AND ANERGY : 自己寛容に関する理論的研究 : 制御性Ｔ細胞とアナジーについて. (Thesis). Kyushu University / 九州大学. Retrieved from http://hdl.handle.net/2324/21712 ; http://dx.doi.org/10.15017/21712

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):

佐伯, 晃一. “THEORETICAL STUDIES OF SELF-TOLERANCE : REGULATORY T CELLS AND ANERGY : 自己寛容に関する理論的研究 : 制御性Ｔ細胞とアナジーについて.” 2013. Thesis, Kyushu University / 九州大学. Accessed March 04, 2021. http://hdl.handle.net/2324/21712 ; http://dx.doi.org/10.15017/21712.

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

MLA Handbook (7^th Edition):

佐伯, 晃一. “THEORETICAL STUDIES OF SELF-TOLERANCE : REGULATORY T CELLS AND ANERGY : 自己寛容に関する理論的研究 : 制御性Ｔ細胞とアナジーについて.” 2013. Web. 04 Mar 2021.

Vancouver:

佐伯 �. THEORETICAL STUDIES OF SELF-TOLERANCE : REGULATORY T CELLS AND ANERGY : 自己寛容に関する理論的研究 : 制御性Ｔ細胞とアナジーについて. [Internet] [Thesis]. Kyushu University / 九州大学; 2013. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/2324/21712 ; http://dx.doi.org/10.15017/21712.

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

Council of Science Editors:

佐伯 �. THEORETICAL STUDIES OF SELF-TOLERANCE : REGULATORY T CELLS AND ANERGY : 自己寛容に関する理論的研究 : 制御性Ｔ細胞とアナジーについて. [Thesis]. Kyushu University / 九州大学; 2013. Available from: http://hdl.handle.net/2324/21712 ; http://dx.doi.org/10.15017/21712

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

Oregon State University

14. Maxwell, Joseph R. The role of costimulation and adjuvants in the development of T cell effector and memory responses.

Degree: PhD, Microbiology, 2001, Oregon State University

URL: http://hdl.handle.net/1957/32495

► T cells are one of the key cells in the immune system. Although they are not the first line of defense against a pathogen, their… (more)

▼ T cells are one of the key cells in the immune system. Although they are not the first line of defense against a pathogen, their functions can greatly enhance the phagocytosis and destruction of pathogens as well as the development of antibody responses. Furthermore, even when responding T cells have facilitated the clearance of the pathogen, they can avoid death to become long-lived cells that "remember" encountering the pathogen for years afterward. This long-term memory allows subsequent immune responses to improve with each exposure, ultimately preventing disease upon reinfection. The activation of these T cells depends on specific recognition of antigen along with a costimulatory signal. This activation process is well studied, but not completely understood. Additionally, the mechanism behind memory T cell development is still very much unknown. In the work presented in this thesis, delivery of costimulatory signals via CD4O and 0X40 were studied using an in vivo superantigen (SAg) model of T cell stimulation. In the context of this two-signal (SAg + costimulation) model, both CD4O and OX40 could deliver signals that enhanced SAg-reactive T cell clonal expansion, but they could only partially prevent T cell death. Coadministration of the inflammatory agent lipopolysaccharide (LPS), however, could keep increased responder T cell populations alive for at least two months. Interestingly, this three-signal (SAg + costimulation + LPS) induced survival was not dependent on proinflammatory cytokines or activation of the transcription factor NF-KB, but was sensitive to the immunosuppressant cyclosporin A (CsA). The mode of action of CsA may point to the mechanism driving long-term T cell survival. Additionally, examination of early time points after three-signal stimulation suggested more clues to the mechanism of survival induction. The cytokines IL-2 and TNF-α seem to be involved early on, but for now, little is known about their complete role. Thus, the goal of this work was to investigate the costimulatory and adjuvant-mediated signals required for memory T cell development. Ultimately, an understanding of how memory T cells can be generated could be used to enhance vaccine efficacy or shut off autoimmune conditions. Advisors/Committee Members: Vella, Anthony T. (advisor).

Subjects/Keywords: T cells

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

APA (6^th Edition):

Maxwell, J. R. (2001). The role of costimulation and adjuvants in the development of T cell effector and memory responses. (Doctoral Dissertation). Oregon State University. Retrieved from http://hdl.handle.net/1957/32495

Chicago Manual of Style (16^th Edition):

Maxwell, Joseph R. “The role of costimulation and adjuvants in the development of T cell effector and memory responses.” 2001. Doctoral Dissertation, Oregon State University. Accessed March 04, 2021. http://hdl.handle.net/1957/32495.

MLA Handbook (7^th Edition):

Maxwell, Joseph R. “The role of costimulation and adjuvants in the development of T cell effector and memory responses.” 2001. Web. 04 Mar 2021.

Vancouver:

Maxwell JR. The role of costimulation and adjuvants in the development of T cell effector and memory responses. [Internet] [Doctoral dissertation]. Oregon State University; 2001. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1957/32495.

Council of Science Editors:

Maxwell JR. The role of costimulation and adjuvants in the development of T cell effector and memory responses. [Doctoral Dissertation]. Oregon State University; 2001. Available from: http://hdl.handle.net/1957/32495

University of Manchester

15. Davies, Sian. T Cell Phenotypes in Upper Gastrointestinal Cancers.

Degree: 2016, University of Manchester

URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:300583

► AbstractBackground: Upper gastrointestinal adenocarcinomas are increasing in prevalence, particularly oesophageal cancer where the incidence rates have increased by over 65% in the last 30 years.… (more)

▼ AbstractBackground: Upper gastrointestinal adenocarcinomas are increasing in prevalence, particularly oesophageal cancer where the incidence rates have increased by over 65% in the last 30 years. Both adenocarcinomas are associated with very poor outcomes; the 5 year survival rate for oesophageal cancer being only 15% and gastric cancer 19%. There has been limited research into the role of the immune system in the development and treatment of upper gastrointestinal adenocarcinomas. Some studies have suggested that certain T helper subsets, including Th17 and Th22 cells, may play a role in these cancers and could therefore be a potential area of further study. However the classification of these cell types has altered over time in part due to the increased availability of marker–specific antibodies and increased power of multi-colour flow cytometry technology. Thus, the limited ability to clearly detect specific T cell subsets in earlier studies may have contributed to the contradictory roles predicted for these T helper subsets cells in the development of upper gastrointestinal malignancy. Aims: This project focuses on developing multi-colour flow cytometry panels that can accurately identify the diversity of T helper cell phenotypes and use these techniques to further explore the role these cells may have in the development and disease process of upper gastrointestinal adenocarcinomas.Methods: Blood samples from healthy donors and patients with either gastric adenocarcinoma or oesophageal adenocarcinoma would be collected and matched peripheral blood mononuclear cells (PBMC) isolated. Experiments were performed to develop an optimized flow cytometry panel that could identify the subtype populations of CD4 cells Th17 and Th22 by varying the duration of activation and the freeze / thawing of the PBMCs. Alongside this process, a flow cytometry technique was developed to optimize the identification of these populations. Once this methodological process was optimised, healthy donor PBMCs and gastric or oesophageal cancer PBMCs were analysed to determine the relative frequency of Th17 and Th22 cells within the different patient and healthy donor cellular populations. Results: The optimal activation period to identification of Th17 and Th22 cells was 16 hours. Moreover, freeze / thawing had minimal impact on the ability to identify these populations thereby facilitating the batched analysis with improved consistency in sample analysis. A flow cytometry panel of 10 flourochromes was also designed and optimised to more accurately improve identification of Th17 and Th22 by their cytokine profiles CD3+CD4+IL17+IL10-INF?- and CD3+CD4+IL22+IL17-TNF?+ respectively. To also identify the possible plastic nature of Th17 cells, further populations were defined by their cytokine profiles Th17/Treg (CD3+CD4+IL-17+IL-10+INF?-) and Th17/Th1 (CD3+CD4+IL-17+IL-10-INF?+). Analyses of these populations in healthy donor PBMCs found a significant positive correlation between the relative frequency of Th17 and Th22 cells, Th17/Th1 and Th22… Advisors/Committee Members: MANSOOR, ABDUL AW, GALLOWAY, SIMON S, Gilham, David, Mansoor, Abdul, Galloway, Simon.

Subjects/Keywords: T Cells; Upper GI Cancers

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

APA (6^th Edition):

Davies, S. (2016). T Cell Phenotypes in Upper Gastrointestinal Cancers. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:300583

Chicago Manual of Style (16^th Edition):

Davies, Sian. “T Cell Phenotypes in Upper Gastrointestinal Cancers.” 2016. Doctoral Dissertation, University of Manchester. Accessed March 04, 2021. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:300583.

MLA Handbook (7^th Edition):

Davies, Sian. “T Cell Phenotypes in Upper Gastrointestinal Cancers.” 2016. Web. 04 Mar 2021.

Vancouver:

Davies S. T Cell Phenotypes in Upper Gastrointestinal Cancers. [Internet] [Doctoral dissertation]. University of Manchester; 2016. [cited 2021 Mar 04]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:300583.

Council of Science Editors:

Davies S. T Cell Phenotypes in Upper Gastrointestinal Cancers. [Doctoral Dissertation]. University of Manchester; 2016. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:300583

Cornell University

16. Carter, Chavez. Role Of Itk In Th17 Mediated Inflammation Model Hypersensitivity Pneumonitis.

Degree: PhD, Immunology, 2015, Cornell University

URL: http://hdl.handle.net/1813/41075

► Hypersensitivity Pneumonitis (HP) is a lung disease caused by repeated inhalation of environmental antigens leading to inflammation, tissue scarring, and some loss of lung function.… (more)

Subjects/Keywords: Itk; Hypersensitivity Pneumonitis; T cells

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

APA (6^th Edition):

Carter, C. (2015). Role Of Itk In Th17 Mediated Inflammation Model Hypersensitivity Pneumonitis. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/41075

Chicago Manual of Style (16^th Edition):

Carter, Chavez. “Role Of Itk In Th17 Mediated Inflammation Model Hypersensitivity Pneumonitis.” 2015. Doctoral Dissertation, Cornell University. Accessed March 04, 2021. http://hdl.handle.net/1813/41075.

MLA Handbook (7^th Edition):

Carter, Chavez. “Role Of Itk In Th17 Mediated Inflammation Model Hypersensitivity Pneumonitis.” 2015. Web. 04 Mar 2021.

Vancouver:

Carter C. Role Of Itk In Th17 Mediated Inflammation Model Hypersensitivity Pneumonitis. [Internet] [Doctoral dissertation]. Cornell University; 2015. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1813/41075.

Council of Science Editors:

Carter C. Role Of Itk In Th17 Mediated Inflammation Model Hypersensitivity Pneumonitis. [Doctoral Dissertation]. Cornell University; 2015. Available from: http://hdl.handle.net/1813/41075

University of Otago

17. Czepluch, Wenzel. Factors mediating successful oral vaccination with lipid-encapsulated Mycobacterium bovis BCG .

Degree: 2012, University of Otago

URL: http://hdl.handle.net/10523/2086

► During the course of this thesis factors mediating successful oral vaccination with lipidencapsulated Mycobacterium bovis BCG were examined. Mice were fed 2x10E07 CFU BCG encapsulated… (more)

▼ During the course of this thesis factors mediating successful oral vaccination with lipidencapsulated Mycobacterium bovis BCG were examined. Mice were fed 2x10E07 CFU BCG encapsulated into a lipid matrix to prevent destruction by the gastrointestinal tract and to allow passage through the gut epithelia. In order to trace the vaccine following oral vaccination, mice were sacrificed at various time points ranging from 6 hours to 8 weeks post vaccination, and macerated lymphatic and non-lymphatic organs plated on solid agar. Initially, BCG was distributed widely in lymphatic and non-lymphatic organs, however, BCG was cleared quickly from most organs and formed small populations of less than 500 CFU/mouse in the mesenteric and cervical lymph nodes, as well as the Peyer’s patches 8 weeks post vaccination. Immuno-histochemistry and confocal microscopy, showed that BCG was absent from the follicles, but instead resided in the T cell containing intra-follicular areas. Very rarely BCG was associated with small CD11b+ cells that did not resemble typical macrophages and lacked peroxidase activity. Instead the majority of BCG could be found forming extracellular groups of 1-4 rods. This was confirmed using cell sorting of leukocytes isolated from alimentary tract lymphatics of orally vaccinated mice and only showed a minority of BCG to be associated with CD11c+ cells. Therefore, BCG is absent from typical antigen presenting cells, but instead might reside in CD11c+CD11b+ myeloid DC. Additionally, Ziehl-Neelsen staining revealed groups of intracellular coccoid forms of BCG. These were located toward the subcapsular space of draining lymph nodes where they were associated with sub-capsular macrophages. Interestingly, cocci proved to be non-platable using solid agar but instead required resuscitation in liquid media and therefore might resemble a form of dormancy. The presence of extracellular rods and intracellular cocci in on-professional antigen presenting cells might highlight the importance of secreted factors as an antigen source promoting successful activation of the immune system. Following oral vaccination, IFN-γ producing cells almost exclusively resided in the spleen. In order to characterize these cells, splenocytes of orally vaccinated mice were isolated 6 weeks post vaccination on the basis of surface marker expression using fluorescence activated cell sorting (FACS). Antigen-specific release of IFN-γ was monitored using ELISA and ELISpot assays and IFN-γ producing T cells were characterized as T effector memory cells expressing CD44, but not CD62L and lacked the expression of mucosal homing markers such as CD103 or α4β7. In addition, Lincoplex assays revealed the production of IL-17 by splenocytes. These did not express CD4+ but rather the γδ T cell eceptor. Together these results show that antigen reservoirs of BCG present in the draining lymphatics contain small numbers of typical filamentous BCG. A larger population of coccoid forms leaves open the possibility that coccoid forms are a major source of antigen… Advisors/Committee Members: McLellan, Alexander Donald (advisor).

Subjects/Keywords: BCG vaccination; T cells DC

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

APA (6^th Edition):

Czepluch, W. (2012). Factors mediating successful oral vaccination with lipid-encapsulated Mycobacterium bovis BCG . (Doctoral Dissertation). University of Otago. Retrieved from http://hdl.handle.net/10523/2086

Chicago Manual of Style (16^th Edition):

Czepluch, Wenzel. “Factors mediating successful oral vaccination with lipid-encapsulated Mycobacterium bovis BCG .” 2012. Doctoral Dissertation, University of Otago. Accessed March 04, 2021. http://hdl.handle.net/10523/2086.

MLA Handbook (7^th Edition):

Czepluch, Wenzel. “Factors mediating successful oral vaccination with lipid-encapsulated Mycobacterium bovis BCG .” 2012. Web. 04 Mar 2021.

Vancouver:

Czepluch W. Factors mediating successful oral vaccination with lipid-encapsulated Mycobacterium bovis BCG . [Internet] [Doctoral dissertation]. University of Otago; 2012. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/10523/2086.

Council of Science Editors:

Czepluch W. Factors mediating successful oral vaccination with lipid-encapsulated Mycobacterium bovis BCG . [Doctoral Dissertation]. University of Otago; 2012. Available from: http://hdl.handle.net/10523/2086

University of Cambridge

18. Alam, Rafeah. T cell phenotyping of a mouse model of Activated PI3Kdelta syndrome.

Degree: PhD, 2019, University of Cambridge

URL: https://www.repository.cam.ac.uk/handle/1810/293595

► Activated PI3Kdelta Syndrome (APDS) is immunodeficiency caused by a heterozygous gain-of-function mutation (E1021K) in the PIK3CD gene, encoding for the p110delta catalytic subunit of phosphoinositide… (more)

Subjects/Keywords: APDS; PI3K; T cells

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APA (6^th Edition):

Alam, R. (2019). T cell phenotyping of a mouse model of Activated PI3Kdelta syndrome. (Doctoral Dissertation). University of Cambridge. Retrieved from https://www.repository.cam.ac.uk/handle/1810/293595

Chicago Manual of Style (16^th Edition):

Alam, Rafeah. “T cell phenotyping of a mouse model of Activated PI3Kdelta syndrome.” 2019. Doctoral Dissertation, University of Cambridge. Accessed March 04, 2021. https://www.repository.cam.ac.uk/handle/1810/293595.

MLA Handbook (7^th Edition):

Alam, Rafeah. “T cell phenotyping of a mouse model of Activated PI3Kdelta syndrome.” 2019. Web. 04 Mar 2021.

Vancouver:

Alam R. T cell phenotyping of a mouse model of Activated PI3Kdelta syndrome. [Internet] [Doctoral dissertation]. University of Cambridge; 2019. [cited 2021 Mar 04]. Available from: https://www.repository.cam.ac.uk/handle/1810/293595.

Council of Science Editors:

Alam R. T cell phenotyping of a mouse model of Activated PI3Kdelta syndrome. [Doctoral Dissertation]. University of Cambridge; 2019. Available from: https://www.repository.cam.ac.uk/handle/1810/293595

University of Cambridge

19. Strege, Katharina. Identifying regulators of cytotoxic T cell function through molecular and genetic screening.

Degree: PhD, 2019, University of Cambridge

URL: https://www.repository.cam.ac.uk/handle/1810/293498https://www.repository.cam.ac.uk/bitstream/1810/293498/2/AppendixB.csv

► Cytotoxic T lymphocytes (CTL) are crucial components of the adaptive immune system that kill infected and tumourigenic cells. CTL killing requires focused secretion of cytotoxic… (more)

▼ Cytotoxic T lymphocytes (CTL) are crucial components of the adaptive immune system that kill infected and tumourigenic cells. CTL killing requires focused secretion of cytotoxic compounds from lytic granules. This process is known as degranulation. In this study, I aimed to establish the CRISPR-Cas9 gene editing technology in primary T cells and to optimise screening approaches to identify regulators of CTL killing. The first half of the thesis focuses on primary mouse CTL. The CRISPR technology was successfully optimised in CTL using Cas9-ribonucleoprotein complexes resulting in efficient CRISPR-mediated loss of target proteins. Genes encoding known mediators of CTL cytotoxicity, \it{Rab27a}, \it{Munc13-4} and \it{Prf1}, were targeted using CRISPR. The resulting samples were used to establish a flow cytometry-based assay that simultaneously measures CTL degranulation and target cell death. This assay enabled me to screen for mediators of CTL killing, while providing mechanistic insight by detecting degranulation. The screen was informed by a transcriptomic study that compared naive and effector CD8 T cells. 1803 significantly upregulated differentially expressed genes [log2(fold change)>2] were identified. Functional annotation analysis and literature research were used to select genes for the targeted CRISPR screen, which highlighted the importance of HIF-1α and NFIL3 in CTL killing. The second half of the thesis focuses on primary human CTL. The combined degranulation and killing assay was further validated using patient-derived CTL, indicating its potential as a diagnostic test. I showed that the assay is suitable for mid-sized screens using a library of 64 compounds targeting the NF-κB signalling pathway. Further opportunities for increasing the scale of this screening technique are discussed. Finally, I successfully tested CRISPR using Cas9-ribonucleoprotein complexes in the human system. Additionally, stable Cas9 expression through lentiviral transduction was explored in primary CTL and related cell lines. This has the potential to allow selection of cells expressing the CRISPR machinery, providing a cleaner experimental system and the possibility of large-scale screening approaches. In summary, the techniques established in this thesis will be valuable for studying the genetics underlying CTL killing and the combined degranulation and killing assay furthermore shows great potential for diagnostic purposes.

Subjects/Keywords: Cytotoxic T cells; CRISPR; screening

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APA (6^th Edition):

Strege, K. (2019). Identifying regulators of cytotoxic T cell function through molecular and genetic screening. (Doctoral Dissertation). University of Cambridge. Retrieved from https://www.repository.cam.ac.uk/handle/1810/293498https://www.repository.cam.ac.uk/bitstream/1810/293498/2/AppendixB.csv

Chicago Manual of Style (16^th Edition):

Strege, Katharina. “Identifying regulators of cytotoxic T cell function through molecular and genetic screening.” 2019. Doctoral Dissertation, University of Cambridge. Accessed March 04, 2021. https://www.repository.cam.ac.uk/handle/1810/293498https://www.repository.cam.ac.uk/bitstream/1810/293498/2/AppendixB.csv.

MLA Handbook (7^th Edition):

Strege, Katharina. “Identifying regulators of cytotoxic T cell function through molecular and genetic screening.” 2019. Web. 04 Mar 2021.

Vancouver:

Strege K. Identifying regulators of cytotoxic T cell function through molecular and genetic screening. [Internet] [Doctoral dissertation]. University of Cambridge; 2019. [cited 2021 Mar 04]. Available from: https://www.repository.cam.ac.uk/handle/1810/293498https://www.repository.cam.ac.uk/bitstream/1810/293498/2/AppendixB.csv.

Council of Science Editors:

Strege K. Identifying regulators of cytotoxic T cell function through molecular and genetic screening. [Doctoral Dissertation]. University of Cambridge; 2019. Available from: https://www.repository.cam.ac.uk/handle/1810/293498https://www.repository.cam.ac.uk/bitstream/1810/293498/2/AppendixB.csv

Columbia University

20. Cvetkovski, Filip. Transcriptional control of tissue-resident memory T cell generation.

Degree: 2019, Columbia University

URL: https://doi.org/10.7916/d8-n16c-b343

► Tissue-resident memory T cells (TRM) are a non-circulating subset of memory that are maintained at sites of pathogen entry and mediate optimal protection against reinfection.… (more)

▼ Tissue-resident memory T cells (TRM) are a non-circulating subset of memory that are maintained at sites of pathogen entry and mediate optimal protection against reinfection. Lung TRM can be generated in response to respiratory infection or vaccination, however, the molecular pathways involved in CD4+TRM establishment have not been defined. Here, we performed transcriptional profiling of influenza-specific lung CD4+TRM following influenza infection to identify pathways implicated in CD4+TRM generation and homeostasis. Lung CD4+TRM displayed a unique transcriptional profile distinct from spleen memory, including up-regulation of a gene network induced by the transcription factor IRF4, a known regulator of effector T cell differentiation. In addition, the gene expression profile of lung CD4+TRM was enriched in gene sets previously described in tissue-resident regulatory T cells. Up-regulation of immunomodulatory molecules such as CTLA-4, PD-1, and ICOS, suggested a potential regulatory role for CD4+TRM in tissues. Using loss-of-function genetic experiments in mice, we demonstrate that IRF4 is required for the generation of lung-localized pathogen-specific effector CD4+T cells during acute influenza infection. Influenza-specific IRF4−/− T cells failed to fully express CD44, and maintained high levels of CD62L compared to wild type, suggesting a defect in complete differentiation into lung-tropic effector T cells. This finding identifies IRF4 as an important regulator of CD4+TRM generation in response to respiratory infection. Furthermore, comparing whole transcriptome profiling of mouse and human lung memory T cell subsets, we define a lung CD4+TRM gene signature common to mice and humans. IRF4 protein was specifically up-regulated in lung CD4+TRM but not in circulating memory subsets, in both humans and mice previously infected with influenza. This result suggest that high expression of IRF4 contributes to a cross-species conserved molecular pathway of long term maintenance of CD4+TRM in the lung. Overall, our findings confirm lung CD4+TRM as a unique memory T cell subset regulated by tissue-specific transcription factors. These results have important implications in focusing future studies of tissue resident memory T cells to factors with translational potential. Importantly, by determining the lung CD4+TRM gene signature common to mice and humans, we motivate future genetic studies that could lead to the complete identification of the mechanisms of TRM maintenance in humans.

Subjects/Keywords: Immunology; T cells; Genetic transcription

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

APA (6^th Edition):

Cvetkovski, F. (2019). Transcriptional control of tissue-resident memory T cell generation. (Doctoral Dissertation). Columbia University. Retrieved from https://doi.org/10.7916/d8-n16c-b343

Chicago Manual of Style (16^th Edition):

Cvetkovski, Filip. “Transcriptional control of tissue-resident memory T cell generation.” 2019. Doctoral Dissertation, Columbia University. Accessed March 04, 2021. https://doi.org/10.7916/d8-n16c-b343.

MLA Handbook (7^th Edition):

Cvetkovski, Filip. “Transcriptional control of tissue-resident memory T cell generation.” 2019. Web. 04 Mar 2021.

Vancouver:

Cvetkovski F. Transcriptional control of tissue-resident memory T cell generation. [Internet] [Doctoral dissertation]. Columbia University; 2019. [cited 2021 Mar 04]. Available from: https://doi.org/10.7916/d8-n16c-b343.

Council of Science Editors:

Cvetkovski F. Transcriptional control of tissue-resident memory T cell generation. [Doctoral Dissertation]. Columbia University; 2019. Available from: https://doi.org/10.7916/d8-n16c-b343

Columbia University

21. Dang, Alex Phu-Cuong. Electrospun antibody-functionalized poly(dimethyl siloxane)-based meshes for improved T cell expansion.

Degree: 2018, Columbia University

URL: https://doi.org/10.7916/D8KW6ZGD

► Adoptive cell transfer (ACT) has garnered significant interest in recent years within the medical field due to its potential in providing an effective form of… (more)

▼ Adoptive cell transfer (ACT) has garnered significant interest in recent years within the medical field due to its potential in providing an effective form of personalized medicine for patients suffering from a wide range of chronic illnesses, including but not limited to cancer. By leveraging the patient’s own cells as the therapeutic agent, concerns over patient compatibility and adverse reactions are significantly reduced. Central to this therapy is the ability to optimize cell quantity and cell activation in order to produce a more robust infusion to the patient. This thesis focuses on two main aspects. The first is the materials synthesis and development of a novel platform for the ex vivo expansion of human T cells for ACT, while the second aims to elucidate the underlying structural mechanics of this platform. This platform, which consists of an electrospun mesh of micron and sub-micron diameter poly (dimethyl siloxane)-based fibers, aims to maintain the high surface-area to volume ratio characteristic of the current clinical gold standard. This also simultaneously allows for effective leveraging of T cell mechanosensing, a phenomenon previously discovered by our lab that is the ability of a human T cell to respond differently to surface mechanical cues. By modulating the concentration of poly (ε-caprolactone) in these fibers, a biocompatible polymer, the mesh mechanical rigidity was varied: this effectively allowed for the leverage of T cell mechanosensing by maintaining a low and tunable Young’s modulus throughout. Additionally, safety concerns involving transfusion of the expansion platform into the patient were addressed by having a single continuous substrate instead of an array of disjoint ferromagnetic beads. Our results thus far indicate that this soft mesh platform can produce upwards of 5.6-12.5 times more T cells in healthy patients than the clinical gold standard while maintaining comparable levels of cellular activation and phenotypic distributions as measured through IFNγ secretion and expression of surface proteins CD107b, CD45RO, and CCR7, respectively. Additionally, this platform demonstrates the ability to produce improved expansion of exhausted (PD-1high) T cells from CLL patients compared to the clinical gold standard across all analyzed Rai stages. Finally, experiments have shown our platform to be scalable to produce clinically relevant levels of cells (> 50 million) from a given starting population, thus indicating its potential in adaptation in larger scale in vitro systems. The currently demonstrated capabilities of our mesh platform thus hold significant promise in the clinical development and adoption of ACT, as well as the development of larger scale in vitro systems. In order to elucidate the underlying structural mechanics of our platform, quantitative AFM studies have indicated a force-dependency in rigidity measurement, thus indicating that standard Hertzian contact models and their derivatives (DMT, Sneddon, etc.), may not be ideal in calculating the rigidity…

Subjects/Keywords: Biomedical engineering; Immunology; T cells

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APA (6^th Edition):

Dang, A. P. (2018). Electrospun antibody-functionalized poly(dimethyl siloxane)-based meshes for improved T cell expansion. (Doctoral Dissertation). Columbia University. Retrieved from https://doi.org/10.7916/D8KW6ZGD

Chicago Manual of Style (16^th Edition):

Dang, Alex Phu-Cuong. “Electrospun antibody-functionalized poly(dimethyl siloxane)-based meshes for improved T cell expansion.” 2018. Doctoral Dissertation, Columbia University. Accessed March 04, 2021. https://doi.org/10.7916/D8KW6ZGD.

MLA Handbook (7^th Edition):

Dang, Alex Phu-Cuong. “Electrospun antibody-functionalized poly(dimethyl siloxane)-based meshes for improved T cell expansion.” 2018. Web. 04 Mar 2021.

Vancouver:

Dang AP. Electrospun antibody-functionalized poly(dimethyl siloxane)-based meshes for improved T cell expansion. [Internet] [Doctoral dissertation]. Columbia University; 2018. [cited 2021 Mar 04]. Available from: https://doi.org/10.7916/D8KW6ZGD.

Council of Science Editors:

Dang AP. Electrospun antibody-functionalized poly(dimethyl siloxane)-based meshes for improved T cell expansion. [Doctoral Dissertation]. Columbia University; 2018. Available from: https://doi.org/10.7916/D8KW6ZGD

University of Oxford

22. Huo, Jiandong. System-level analysis of early signalling in T cells.

Degree: PhD, 2012, University of Oxford

URL: http://ora.ox.ac.uk/objects/uuid:dcff1741-bd39-4b5b-a11b-99277d55890d ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.588401

► The prevailing view of signal transduction is that it proceeds through the linear relay of information via sequential bimolecular interactions, involving, for example, Src homology… (more)

▼ The prevailing view of signal transduction is that it proceeds through the linear relay of information via sequential bimolecular interactions, involving, for example, Src homology (SH) 2 domains. It has been assumed that such interactions are highly selective, i.e. that the affinities of these interactions are several orders of magnitude higher than that for non-specific interactions. However, recent studies have suggested that the difference in affinities between so-called specific and non-specific interactions is not sufficient to support such a proposal. This therefore raises the question of how signalling pathway specificity is generated at all. To address this, we have taken a systems approach by expressing and purifying >90% of the SH2 domains identified in a T cell line using a next-generation sequencing-based transcriptomic analysis, and performed a systematic survey of the interaction of these SH2 domains with a set of potential phosphorylated peptides derived from the key signalling receptors of the T cell (including CD28, CTLA-4, PD-1, ICOS, BTLA, LAT and the CD3 subunits of the TCR complex), using surface plasmon resonance-based binding assays. Our results show that, instead of being highly selective for certain SH2 domains, the T cell-expressed receptors are very cross-reactive, such that each receptor is found to interact with ~50 different SH2 domains on average. In silico analysis based on these results confirms the expectation that affinity itself is not the sole determining factor for receptor specificity. Further exploration of the system using in silico simulations incorporating the absolute concentrations of SH2 domain-containing proteins measured in T cells using a proteomics-based approach, suggests instead that the specificity of SH2 domain recruitment by T-cell receptors is the result of systems effects, with expression levels of the signalling proteins being a major factor. Surprisingly, LCK, the most highly expressed SH2 domain in resting Jurkat, is predicted to dominate the binding of most receptors, suggesting a novel mechanism of Src kinase activation and function.

Subjects/Keywords: 571.966; Immunology; signalling; T cells

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APA (6^th Edition):

Huo, J. (2012). System-level analysis of early signalling in T cells. (Doctoral Dissertation). University of Oxford. Retrieved from http://ora.ox.ac.uk/objects/uuid:dcff1741-bd39-4b5b-a11b-99277d55890d ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.588401

Chicago Manual of Style (16^th Edition):

Huo, Jiandong. “System-level analysis of early signalling in T cells.” 2012. Doctoral Dissertation, University of Oxford. Accessed March 04, 2021. http://ora.ox.ac.uk/objects/uuid:dcff1741-bd39-4b5b-a11b-99277d55890d ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.588401.

MLA Handbook (7^th Edition):

Huo, Jiandong. “System-level analysis of early signalling in T cells.” 2012. Web. 04 Mar 2021.

Vancouver:

Huo J. System-level analysis of early signalling in T cells. [Internet] [Doctoral dissertation]. University of Oxford; 2012. [cited 2021 Mar 04]. Available from: http://ora.ox.ac.uk/objects/uuid:dcff1741-bd39-4b5b-a11b-99277d55890d ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.588401.

Council of Science Editors:

Huo J. System-level analysis of early signalling in T cells. [Doctoral Dissertation]. University of Oxford; 2012. Available from: http://ora.ox.ac.uk/objects/uuid:dcff1741-bd39-4b5b-a11b-99277d55890d ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.588401

23. Prodger, Jessica L. Defining Immune Correlates of HIV Susceptibility in the Foreskin.

Degree: 2014, University of Toronto

URL: http://hdl.handle.net/1807/65727

►

HIV is a predominantly sexually transmitted infection that has infected over 60 million people and been responsible for 60 million deaths. To date, non-antiretroviral microbicides… (more)

▼

HIV is a predominantly sexually transmitted infection that has infected over 60 million people and been responsible for 60 million deaths. To date, non-antiretroviral microbicides have failed to prevent HIV acquisition, or even increased it. This is likely because HIV preferentially infects activated immune cells (CD4+ T cells), taking advantage of the body’s attempts to defend itself. Therefore, relative immunoquiescence, as opposed to immune activation, may be protective. I hypothesized that men who are biologically more susceptible to HIV would have increased foreskin CD4 T cell activation, while the opposite would be true of men who are relatively resistant. The foreskin has recently been identified as a major site of HIV acquisition, but little previous research has been performed on this tissue. I therefore developed novel techniques to isolate viable, immunologically functional T cells from foreskin tissue. I then worked with the Rakai Health Sciences Program in Uganda to identify men undergoing elective circumcision who are HIV-Exposed but have remained SeroNegative (HESN, relatively resistant to HIV), and men with Herpes Simple Virus-2 infection (HSV-2+, relatively susceptible to HIV). I collected sub-preputial swabs and foreskin tissue from these men, and characterized numerous immune parameters in their samples. I found that HSV-2+ men had an increased relative abundance of CD4 T cells co-expressing the HIV receptor CCR5. In contrast, I found that HESN men had a decreased relative abundance of activated T cells (CD4/8 T cells producing TNFα) and Th17 cells (a pro-inflammatory T cell subset known to be particularly susceptible to HIV). Additionally, foreskin secretions from HESN men were more likely to have antibodies (IgA) able to neutralize HIV, and had more innate anti-viral peptides. I therefore propose HIV resistance may be driven by decreased T cell activation in genital tissue, in combination with increased secretion of anti-HIV immune proteins.

PhD

Advisors/Committee Members: Kaul, Rupert, Medical Science.

Subjects/Keywords: HIV; T cells; Circumcision; 0379

10 more images…

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APA (6^th Edition):

Prodger, J. L. (2014). Defining Immune Correlates of HIV Susceptibility in the Foreskin. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/65727

Chicago Manual of Style (16^th Edition):

Prodger, Jessica L. “Defining Immune Correlates of HIV Susceptibility in the Foreskin.” 2014. Doctoral Dissertation, University of Toronto. Accessed March 04, 2021. http://hdl.handle.net/1807/65727.

MLA Handbook (7^th Edition):

Prodger, Jessica L. “Defining Immune Correlates of HIV Susceptibility in the Foreskin.” 2014. Web. 04 Mar 2021.

Vancouver:

Prodger JL. Defining Immune Correlates of HIV Susceptibility in the Foreskin. [Internet] [Doctoral dissertation]. University of Toronto; 2014. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1807/65727.

Council of Science Editors:

Prodger JL. Defining Immune Correlates of HIV Susceptibility in the Foreskin. [Doctoral Dissertation]. University of Toronto; 2014. Available from: http://hdl.handle.net/1807/65727

University of Melbourne

24. Lin, Wen Xu. Study of regulatory T cells in transplantation.

Degree: 2011, University of Melbourne

URL: http://hdl.handle.net/11343/36958

► Transplantation has prolonged the survival of patients with terminal organ diseases. However, even with today’s advanced immunosuppressive therapies, graft rejection remains a major concern with… (more)

▼ Transplantation has prolonged the survival of patients with terminal organ diseases. However, even with today’s advanced immunosuppressive therapies, graft rejection remains a major concern with significant patient morbidity and mortality still being associated with immunosuppressive medications. Tolerance induction has been a goal in transplantation for many years, although it still remains elusive. Recently, interest has been renewed in a subset of T cells, the regulatory T cells (Treg) and their potential role in tolerance induction. These cells demonstrate immunosuppressive potential in experimental models. This thesis focuses on examining the role of Treg in transplantation. Techniques to characterise and genetically engineer Treg in vitro were developed. Our studies in over 200 transplant recipients (renal and liver) have shown: (1) percentages of CD4+CD25+ (“activated”) cells and CD4+CD25+Foxp3+ cells are significantly lower in RTR compared to controls; (2) percentages of “activated” cells are significantly lower in LTR compared to controls, while the percentages of CD4+CD25+Foxp3+ cells are significantly higher in patients with chronic liver diseases and LTR compared to normal controls; (3) the key finding that the proportion of “activated” cells expressing Foxp3+ cells is higher in RTR and correlates with renal allograft function; (4) the proportion of CD4+CD25+Foxp3+ cells do not alter at different times post-transplant; (5) a higher percentage of CD4+CD25+ cells is observed in recipients with malignancy; (6) incorporation of human Foxp3 in a human T cell line, CEM may induce a Treg-like phenotype. Collectively, the results from this project provide significant insight into the role of Treg in clinical transplantation and the role of the important Treg transcriptional regulator, Foxp3, in Treg induction and developing therapeutic strategies to facilitate graft acceptance by extending the use of Treg in the future. These findings may help to add further information regarding the mechanism of tolerance induction that may lead to graft survival without ongoing drug therapy.

Subjects/Keywords: regulatory T cells; transplantation

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APA (6^th Edition):

Lin, W. X. (2011). Study of regulatory T cells in transplantation. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/36958

Chicago Manual of Style (16^th Edition):

Lin, Wen Xu. “Study of regulatory T cells in transplantation.” 2011. Doctoral Dissertation, University of Melbourne. Accessed March 04, 2021. http://hdl.handle.net/11343/36958.

MLA Handbook (7^th Edition):

Lin, Wen Xu. “Study of regulatory T cells in transplantation.” 2011. Web. 04 Mar 2021.

Vancouver:

Lin WX. Study of regulatory T cells in transplantation. [Internet] [Doctoral dissertation]. University of Melbourne; 2011. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/11343/36958.

Council of Science Editors:

Lin WX. Study of regulatory T cells in transplantation. [Doctoral Dissertation]. University of Melbourne; 2011. Available from: http://hdl.handle.net/11343/36958

University of Melbourne

25. Ross, Ellen Margaret. Autoantigen-specific regulatory T cells in autoimmunity.

Degree: 2012, University of Melbourne

URL: http://hdl.handle.net/11343/38044

► In order to protect the host from disease, the immune system is equipped with the capacity to recognise and respond to a plethora of pathogens.… (more)

▼ In order to protect the host from disease, the immune system is equipped with the capacity to recognise and respond to a plethora of pathogens. Given the breadth of the specificities that the immune system will react to, it is remarkable that the tissues and organs that constitute self avoid immune-mediated damage. Injury to self does not occur because the immune systemic is educated, through a variety of mechanisms, to distinguish between antigens that constitute self and those antigens that are foreign, a collective process which is termed immune tolerance. Immune tolerance is an extremely important process, as made most evident by the development of immune-mediated damage and autoimmune disease that occurs when immune tolerance is not upheld, the outcomes of which can be potentially catastrophic. Understanding the intricacies of immune tolerance will be beneficial in discerning why some individuals develop autoimmune disease, and will also aid in the identification of strategies which can potentially be utilised for the treatment of autoimmune disease. Experimental autoimmune gastritis in mice is an excellent model of human autoimmune gastritis and is therefore a useful tool for the study of autoimmune disease and tolerance. Experimental autoimmune gastritis is a very well characterised disease, as the molecular, cellular and genetic aspects of the disease have been well studied. The disease is characterised by a CD4+ T cell mediated immune response that is directed towards the α and β subunits of the gastric H+/K+-ATPase, which is the autoantigen target in both murine and human autoimmune gastritis. Within the thymus, expression of the H/Kβ is, at best, barely detectable, and this compromises the presentation of H/Kα, which is unstable and therefore rapidly degraded in the absence of H/Kβ. As a result, thymic events appear to contribute little in the maintenance of tolerance to the H+/K+-ATPase, and for this reason it is likely that tolerogenic events in the periphery will be paramount. An important component of peripheral tolerance is the regulatory T cell population, as these cells are required throughout life to maintain peripheral immune homeostasis in order to avoid the development of autoimmunity. Regulatory T cells may well be important in maintaining peripheral tolerance to the H+/K+-ATPase given the lack of thymic tolerogenic events that occur in response to this autoantigen. The aim of this investigation was to investigate the role of regulatory T cells in maintaining tolerance to the H+/K+-ATPase. The work presented in Chapter 3 reaffirms that H/Kα-specific regulatory T cells do not develop with the thymus, but instead can be generated de novo in the periphery following contact with the H/Kα. Induced H/Kα-specific regulatory T cells are shown to be suppressive and following this, an investigation into the mechanisms that drive the extrathymic generation of H/Kα-specific regulatory T cells indicated that…

Subjects/Keywords: regulatory T cells; autoimmunity; tolerance

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APA (6^th Edition):

Ross, E. M. (2012). Autoantigen-specific regulatory T cells in autoimmunity. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/38044

Chicago Manual of Style (16^th Edition):

Ross, Ellen Margaret. “Autoantigen-specific regulatory T cells in autoimmunity.” 2012. Doctoral Dissertation, University of Melbourne. Accessed March 04, 2021. http://hdl.handle.net/11343/38044.

MLA Handbook (7^th Edition):

Ross, Ellen Margaret. “Autoantigen-specific regulatory T cells in autoimmunity.” 2012. Web. 04 Mar 2021.

Vancouver:

Ross EM. Autoantigen-specific regulatory T cells in autoimmunity. [Internet] [Doctoral dissertation]. University of Melbourne; 2012. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/11343/38044.

Council of Science Editors:

Ross EM. Autoantigen-specific regulatory T cells in autoimmunity. [Doctoral Dissertation]. University of Melbourne; 2012. Available from: http://hdl.handle.net/11343/38044

University of Cambridge

26. Strege, Katharina. Identifying regulators of cytotoxic T cell function through molecular and genetic screening.

Degree: PhD, 2019, University of Cambridge

URL: https://doi.org/10.17863/CAM.40639 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.782806

► Cytotoxic T lymphocytes (CTL) are crucial components of the adaptive immune system that kill infected and tumourigenic cells. CTL killing requires focused secretion of cytotoxic… (more)

▼ Cytotoxic T lymphocytes (CTL) are crucial components of the adaptive immune system that kill infected and tumourigenic cells. CTL killing requires focused secretion of cytotoxic compounds from lytic granules. This process is known as degranulation. In this study, I aimed to establish the CRISPR-Cas9 gene editing technology in primary T cells and to optimise screening approaches to identify regulators of CTL killing. The first half of the thesis focuses on primary mouse CTL. The CRISPR technology was successfully optimised in CTL using Cas9-ribonucleoprotein complexes resulting in efficient CRISPR-mediated loss of target proteins. Genes encoding known mediators of CTL cytotoxicity, Rab27a Munc13-4 and Prf1, were targeted using CRISPR. The resulting samples were used to establish a flow cytometry-based assay that simultaneously measures CTL degranulation and target cell death. This assay enabled me to screen for mediators of CTL killing, while providing mechanistic insight by detecting degranulation. The screen was informed by a transcriptomic study that compared naive and effector CD8 T cells. 1803 significantly upregulated differentially expressed genes [log2(fold change) > 2] were identified. Functional annotation analysis and literature research were used to select genes for the targeted CRISPR screen, which highlighted the importance of HIF-1α and NFIL3 in CTL killing. The second half of the thesis focuses on primary human CTL. The combined degranulation and killing assay was further validated using patient-derived CTL, indicating its potential as a diagnostic test. I showed that the assay is suitable for mid-sized screens using a library of 64 compounds targeting the NF-κB signalling pathway. Further opportunities for increasing the scale of this screening technique are discussed. Finally, I successfully tested CRISPR using Cas9-ribonucleoprotein complexes in the human system. Additionally, stable Cas9 expression through lentiviral transduction was explored in primary CTL and related cell lines. This has the potential to allow selection of cells expressing the CRISPR machinery, providing a cleaner experimental system and the possibility of large-scale screening approaches. In summary, the techniques established in this thesis will be valuable for studying the genetics underlying CTL killing and the combined degranulation and killing assay furthermore shows great potential for diagnostic purposes.

Subjects/Keywords: Cytotoxic T cells; CRISPR; screening

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APA (6^th Edition):

Strege, K. (2019). Identifying regulators of cytotoxic T cell function through molecular and genetic screening. (Doctoral Dissertation). University of Cambridge. Retrieved from https://doi.org/10.17863/CAM.40639 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.782806

Chicago Manual of Style (16^th Edition):

Strege, Katharina. “Identifying regulators of cytotoxic T cell function through molecular and genetic screening.” 2019. Doctoral Dissertation, University of Cambridge. Accessed March 04, 2021. https://doi.org/10.17863/CAM.40639 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.782806.

MLA Handbook (7^th Edition):

Strege, Katharina. “Identifying regulators of cytotoxic T cell function through molecular and genetic screening.” 2019. Web. 04 Mar 2021.

Vancouver:

Strege K. Identifying regulators of cytotoxic T cell function through molecular and genetic screening. [Internet] [Doctoral dissertation]. University of Cambridge; 2019. [cited 2021 Mar 04]. Available from: https://doi.org/10.17863/CAM.40639 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.782806.

Council of Science Editors:

Strege K. Identifying regulators of cytotoxic T cell function through molecular and genetic screening. [Doctoral Dissertation]. University of Cambridge; 2019. Available from: https://doi.org/10.17863/CAM.40639 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.782806

University of Cambridge

27. Alam, Rafeah. T cell phenotyping of a mouse model of Activated PI3Kdelta Syndrome.

Degree: PhD, 2019, University of Cambridge

URL: https://doi.org/10.17863/CAM.40724 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.782758

► Activated PI3Kdelta Syndrome (APDS) is immunodeficiency caused by a heterozygous gain-of-function mutation (E1021K) in the PIK3CD gene, encoding for the p110delta catalytic subunit of phosphoinositide… (more)

Subjects/Keywords: APDS; PI3K; T cells

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APA (6^th Edition):

Alam, R. (2019). T cell phenotyping of a mouse model of Activated PI3Kdelta Syndrome. (Doctoral Dissertation). University of Cambridge. Retrieved from https://doi.org/10.17863/CAM.40724 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.782758

Chicago Manual of Style (16^th Edition):

Alam, Rafeah. “T cell phenotyping of a mouse model of Activated PI3Kdelta Syndrome.” 2019. Doctoral Dissertation, University of Cambridge. Accessed March 04, 2021. https://doi.org/10.17863/CAM.40724 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.782758.

MLA Handbook (7^th Edition):

Alam, Rafeah. “T cell phenotyping of a mouse model of Activated PI3Kdelta Syndrome.” 2019. Web. 04 Mar 2021.

Vancouver:

Alam R. T cell phenotyping of a mouse model of Activated PI3Kdelta Syndrome. [Internet] [Doctoral dissertation]. University of Cambridge; 2019. [cited 2021 Mar 04]. Available from: https://doi.org/10.17863/CAM.40724 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.782758.

Council of Science Editors:

Alam R. T cell phenotyping of a mouse model of Activated PI3Kdelta Syndrome. [Doctoral Dissertation]. University of Cambridge; 2019. Available from: https://doi.org/10.17863/CAM.40724 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.782758

University of Montana

28. Osborne, Douglas Grant. Biological effects of trogocytosis on CD4+ T lymphocytes.

Degree: PhD, 2013, University of Montana

URL: https://scholarworks.umt.edu/etd/100

► Antigen recognition by CD4+ T cells leads to large-scale spatial and temporal molecular redistributions, forming the immunological synapse. We have previously shown that upon… (more)

Subjects/Keywords: T cells; trogocytosis; CD4; imaging

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

APA (6^th Edition):

Osborne, D. G. (2013). Biological effects of trogocytosis on CD4+ T lymphocytes. (Doctoral Dissertation). University of Montana. Retrieved from https://scholarworks.umt.edu/etd/100

Chicago Manual of Style (16^th Edition):

Osborne, Douglas Grant. “Biological effects of trogocytosis on CD4+ T lymphocytes.” 2013. Doctoral Dissertation, University of Montana. Accessed March 04, 2021. https://scholarworks.umt.edu/etd/100.

MLA Handbook (7^th Edition):

Osborne, Douglas Grant. “Biological effects of trogocytosis on CD4+ T lymphocytes.” 2013. Web. 04 Mar 2021.

Vancouver:

Osborne DG. Biological effects of trogocytosis on CD4+ T lymphocytes. [Internet] [Doctoral dissertation]. University of Montana; 2013. [cited 2021 Mar 04]. Available from: https://scholarworks.umt.edu/etd/100.

Council of Science Editors:

Osborne DG. Biological effects of trogocytosis on CD4+ T lymphocytes. [Doctoral Dissertation]. University of Montana; 2013. Available from: https://scholarworks.umt.edu/etd/100

University of New South Wales

29. Pollock, Abigail Hazel. How dietary lipids and membrane order affect T cell function in vivo.

Degree: Centre for Vascular Research, 2013, University of New South Wales

URL: http://handle.unsw.edu.au/1959.4/53561 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:12258/SOURCE02?view=true

► As the T cell receptor and many of the associated signalling molecules are embedded within the plasma membrane, it has been hypothesised that plasma membrane… (more)

▼ As the T cell receptor and many of the associated signalling molecules are embedded within the plasma membrane, it has been hypothesised that plasma membrane lipids, and associated lipid ‘ordered’ membrane domains, play a role in regulating T cell signalling. The first aim of this thesis was to examine in mice whether dietary lipids influence the lipid composition of T cells and thus membrane order, and how this correlates to in vivo and ex vivo T cell responses. Chapters 3 and 4 describe both acute and long-term dietary studies, which involved feeding C57BL/6J and LDLR-/- mice a high-fat or high-cholesterol diet. A contact hypersensitivity (CHS) reaction was then induced using 1-fluoro-2,4-dinitrobenzene and the CD4+ and CD8+ T cell responses examined in the draining lymph nodes by flow cytometry. The in vivo T cell responses were correlated to the cellular lipid content of splenic T cells using mass spectrometry, and membrane order measured with Laurdan microscopy. Finally, the activation response of ex vivo stimulated splenic T cells was assessed with qRT-PCR. Both the C57BL/6J and LDLR-/- dietary studies illustrated that long-term high-fat or high-cholesterol feeding significantly increased both CD4+ and CD8+ T cell proliferation, and central-memory CD4+ T cell production, within the draining lymph nodes following CHS. This was associated with changes in cellular phospholipids, fatty acids and cholesterol, as well as alterations in membrane order at the T cell activation site, and reduced IL-2 mRNA production. The last results chapter of this thesis, chapter 5, focused directly on how membrane order impacts on T cell function in vivo. Using an adoptive transfer system, CD4+ T cells from OT-II transgenic mice were treated with the oxysterol 7-ketocholesterol, which perturbs membrane condensation, or a cholesterol control, before transfer into B6.SJL recipient mice. I then challenged the recipients with ovalbumin323–339 to measure antigen-specific CD4+ T cell responses by flow cytometry, which were again correlated the sterol content of ex vivo manipulated cells. Our results were inconsistent but suggest that both 7KC and cholesterol treatment cause a reduction in OVA-specific CD4+ T cell proliferation within the draining lymph nodes of recipient mice. Advisors/Committee Members: Gaus, Katharina, Centre for Vascular Research, Faculty of Medicine, UNSW, Tedla, Nicodemus, Faculty of Medicine, UNSW.

Subjects/Keywords: Lipids; T cells; Membrane order

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APA (6^th Edition):

Pollock, A. H. (2013). How dietary lipids and membrane order affect T cell function in vivo. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/53561 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:12258/SOURCE02?view=true

Chicago Manual of Style (16^th Edition):

Pollock, Abigail Hazel. “How dietary lipids and membrane order affect T cell function in vivo.” 2013. Doctoral Dissertation, University of New South Wales. Accessed March 04, 2021. http://handle.unsw.edu.au/1959.4/53561 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:12258/SOURCE02?view=true.

MLA Handbook (7^th Edition):

Pollock, Abigail Hazel. “How dietary lipids and membrane order affect T cell function in vivo.” 2013. Web. 04 Mar 2021.

Vancouver:

Pollock AH. How dietary lipids and membrane order affect T cell function in vivo. [Internet] [Doctoral dissertation]. University of New South Wales; 2013. [cited 2021 Mar 04]. Available from: http://handle.unsw.edu.au/1959.4/53561 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:12258/SOURCE02?view=true.

Council of Science Editors:

Pollock AH. How dietary lipids and membrane order affect T cell function in vivo. [Doctoral Dissertation]. University of New South Wales; 2013. Available from: http://handle.unsw.edu.au/1959.4/53561 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:12258/SOURCE02?view=true

University of Aberdeen

30. Pappalardo, Angela. Defining the role of γδ cells in bone loss associated with chronic inflammation.

Degree: PhD, 2013, University of Aberdeen

URL: https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12152657240005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.589513

► The extensive infiltration of immune cells in the joints of patients affected by rheumatoid arthritis (RA), and the subsequent production of pro-inflammatory cytokines triggers bone… (more)

Subjects/Keywords: 616.7; Osteoclast inhibition; T cells

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

APA (6^th Edition):

Pappalardo, A. (2013). Defining the role of γδ cells in bone loss associated with chronic inflammation. (Doctoral Dissertation). University of Aberdeen. Retrieved from https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12152657240005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.589513

Chicago Manual of Style (16^th Edition):

Pappalardo, Angela. “Defining the role of γδ cells in bone loss associated with chronic inflammation.” 2013. Doctoral Dissertation, University of Aberdeen. Accessed March 04, 2021. https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12152657240005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.589513.

MLA Handbook (7^th Edition):

Pappalardo, Angela. “Defining the role of γδ cells in bone loss associated with chronic inflammation.” 2013. Web. 04 Mar 2021.

Vancouver:

Pappalardo A. Defining the role of γδ cells in bone loss associated with chronic inflammation. [Internet] [Doctoral dissertation]. University of Aberdeen; 2013. [cited 2021 Mar 04]. Available from: https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12152657240005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.589513.

Council of Science Editors:

Pappalardo A. Defining the role of γδ cells in bone loss associated with chronic inflammation. [Doctoral Dissertation]. University of Aberdeen; 2013. Available from: https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12152657240005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.589513

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