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University of Melbourne
1.
CAMERON, GARTH.
NKT cell glycolipid recognition and response.
Degree: 2013, University of Melbourne
URL: http://hdl.handle.net/11343/38542 
► NKT cells are a subset of T lymphocytes that influence an array of immune response ranging from infection, to autoimmunity and cancer. NKT cell-mediated immune…
(more)
▼ NKT cells are a subset of T lymphocytes that influence an array of immune response ranging from infection, to autoimmunity and cancer. NKT cell-mediated immune intervention has displayed considerable promise in the context of cancer, and there is great hope that this population will ultimately provide a novel form of immunotherapy for this disease. However, this requires a greater understanding of NKT cell recognition of α-GalCer and its analogues, especially those that are capable of biasing the cytokine response. Similarly, our understanding of NKT cell recognition of self-antigens, including tumour-associated ligands is currently limited.
Closely related CD1d-restricted glycolipid antigens can bias the NKT cell response towards the production of either Th1- or Th2-type cytokines, which has created great interest in potential improvements to NKT cell-mediated therapy, however the molecular basis for this altered responsiveness is unclear. The first chapter of this thesis demonstrated that modifications amongst Th2 biasing NKT cell agonists [OCH and α-GalCer (C20:2)] had limited impact on TCR interactions, whilst reducing proliferative potency, indicating differences in ligand processing and presentation. Alteration of the glycosidic linkage within the Th1 biasing analogue α-C-GalCer reduced the t1/2 of the interaction, inhibiting IFN-γ production from NKT cells, whilst maintain a systemic Th1 bias. These data demonstrating that the Th bias of the prototypic Th1 and Th2 biasing NKT cells ligands are primarily related to their altered pharmacokinetic properties. However, this study has also shown that modification of the glycolipid sugar residue has a marked impact on TCR interactions and the quantity and quality of the NKT cell cytokine response, suggesting that both pharmacokinetic factors and molecular interactions may be manipulated in tandem to further enhance the therapeutic benefit of NKT cell agonists.
In the second chapter, the studies focused on the role of NKT cell TCR diversity on differential antigen recognition. NKT cells express a semi-invariant TCR, composed of an invariant α-chain, paired with a limited array of Vβ gene segments. Despite the TCR β-chain not interacting directly with glycolipid antigen, this study has shown that diversity within the NKT cell TCR repertoire results in the restricted recognition of the mammalian glycolipid iGb3. Furthermore, the impact of β-chain composition was found to be antigen dependent, suggesting that the β-chain can indirectly impact α-chain contacts with glycolipid. The presence of differential antigen recognition was also observed in relation to the novel Vα10-Jα50 NKT cell population, which displayed an altered recognition hierarchy in relation to Vα14-Jα18 NKT cells, including enhanced reactivity to a bacterial α-glucuronosyl diacylglycerol, supporting an immunological role for NKT cell TCR diversity.
In the final chapter,…
Subjects/Keywords: NKT cells; NKT cell TCR diversity; NKT cell antigens; NKT cell subsets
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APA (6th Edition):
CAMERON, G. (2013). NKT cell glycolipid recognition and response. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/38542
Chicago Manual of Style (16th Edition):
CAMERON, GARTH. “NKT cell glycolipid recognition and response.” 2013. Doctoral Dissertation, University of Melbourne. Accessed April 17, 2021.
http://hdl.handle.net/11343/38542.
MLA Handbook (7th Edition):
CAMERON, GARTH. “NKT cell glycolipid recognition and response.” 2013. Web. 17 Apr 2021.
Vancouver:
CAMERON G. NKT cell glycolipid recognition and response. [Internet] [Doctoral dissertation]. University of Melbourne; 2013. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/11343/38542.
Council of Science Editors:
CAMERON G. NKT cell glycolipid recognition and response. [Doctoral Dissertation]. University of Melbourne; 2013. Available from: http://hdl.handle.net/11343/38542
University of Melbourne
2.
Ross, Fiona Jean.
NKT cell activation by diverse antigens and antigen-presenting cells.
Degree: 2013, University of Melbourne
URL: http://hdl.handle.net/11343/38639
► NKT cells are CD1d-restricted T lymphocytes that have a regulatory role in numerous diseases, which is dependent on their ability to produce Th1, Th2 and…
(more)
▼ NKT cells are CD1d-restricted T lymphocytes that have a regulatory role in numerous diseases, which is dependent on their ability to produce Th1, Th2 and Th17 cytokines. Activation and expansion of NKT cells by their prototypic ligand, α-GalCer, has been trialed in immunotherapies; yet these therapies can potentially be improved by enhancing NKT cell activation or biasing the cytokine response. It is thus important to understand the functional consequences of NKT cell activation by diverse antigens and APC types, as both these factors can influence the response. Furthermore, a thorough understanding of the fine-specificity of the human NKT TCR is required for the effective synthesis of novel NKT cell ligands, and also to uncover self-antigens that can be recognised during disease, infection, and NKT cell development.
A range of APC appear to be capable of activating NKT cells, and have been suggested to influence the quality and magnitude of the response. Chapter 3 demonstrated that splenic DC, B cells and macrophages differed in their ability to activate NKT cells in vitro. A key finding was that in contrast to DN and CD4+ DC, CD8+ DC preferentially induced a Th1 bias from NKT cells, which was attributed to variable co-stimulatory factors between the DC subsets. In contrast, the injection of APC into mice induced a similar response from NKT cells regardless of the APC type. Therefore, different APC were capable of influencing the NKT cell response in vitro, but not in vivo, and this knowledge can be used to help inform us about the NKT/APC interaction during disease, immunotherapies and vaccines.
The recognition of phospholipid self-antigens is thought to be an important aspect of NKT cell biology, although has predominately been demonstrated by NKT cell lines and hybridomas, or during diseased states. Chapter 4 aimed to investigate the extent of phospholipid-reactivity in mice during steady-state conditions. A small proportion of thymic NKT cells were weakly activated following exposure to phospholipids, and their TCR sequences were isolated and cell lines generated to further explore their reactivity. The ether-bonded phospholipid, pLPE, has been shown to potently activate mouse NKT cells and was implicated in NKT cell development. Our result demonstrated that pLPE did not appear to be a strong agonist for thymic NKT cells, yet could activate a Type II NKT cell hybridoma and select Type I NKT cell lines. These results suggest that phospholipids are, at best, much weaker self-antigens for NKT cells than glycolipid antigens, although inflammation triggered during disease or infection may be sufficient to overcome the low reactivity to these antigens.
For the synthesis of optimal human NKT cell ligands it is important to understand the fine-specificity of the mouse and human NKT TCRs. Chapter 5 demonstrated that, unlike mouse NKT cells, human NKT cell activation was critically…
Subjects/Keywords: NKT cells; antigens; antigen-presenting cells
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APA (6th Edition):
Ross, F. J. (2013). NKT cell activation by diverse antigens and antigen-presenting cells. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/38639
Chicago Manual of Style (16th Edition):
Ross, Fiona Jean. “NKT cell activation by diverse antigens and antigen-presenting cells.” 2013. Doctoral Dissertation, University of Melbourne. Accessed April 17, 2021.
http://hdl.handle.net/11343/38639.
MLA Handbook (7th Edition):
Ross, Fiona Jean. “NKT cell activation by diverse antigens and antigen-presenting cells.” 2013. Web. 17 Apr 2021.
Vancouver:
Ross FJ. NKT cell activation by diverse antigens and antigen-presenting cells. [Internet] [Doctoral dissertation]. University of Melbourne; 2013. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/11343/38639.
Council of Science Editors:
Ross FJ. NKT cell activation by diverse antigens and antigen-presenting cells. [Doctoral Dissertation]. University of Melbourne; 2013. Available from: http://hdl.handle.net/11343/38639
Universiteit Utrecht
3.
Vrugt, A.M. van de.
Natural Killer T cells and their functions in atherosclerosis and obesity: a therapeutic perspective for cardiovascular diseases.
Degree: 2014, Universiteit Utrecht
URL: http://dspace.library.uu.nl:8080/handle/1874/301208
► Atherosclerosis and obesity, both related to the development of cardiovascular diseases (CVDs), are increasing pathologies under the global population. Therefore, both pathologies contribute to the…
(more)
▼ Atherosclerosis and obesity, both related to the development of cardiovascular diseases (CVDs), are increasing pathologies under the global population. Therefore, both pathologies contribute to the growing problem of CVDs. In both pathologies, chronic inflammation is the key process that exacerbates disease progression. Natural Killer T (
NKT)
cells are of interest, because these immune
cells connect innate and adaptive immunity. Moreover,
NKT cells get activated by lipid antigens. These antigens are highly enriched in both atherosclerotic lesions and adipose tissue. An obvious role for these
cells in these pathologies has been determined and several pathways involved in these pathologies are known to induce
NKT cell activation and modulate
NKT cell effector function. However, conflicting results make it hard to address whether the effects achieved by
NKT cells are beneficial or pathologic. Therefore, more studies are required that take the role of interfering factors into account, such as the effect of subtypes, environment, and time span. Thereafter, the potential of the
NKT cells for therapeutic application in CVD can be determined.
Advisors/Committee Members: Kalkhoven, E..
Subjects/Keywords: NKT cells; Lipids; Cardiovascular Diseases; Atherosclerosis; Obesity
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APA (6th Edition):
Vrugt, A. M. v. d. (2014). Natural Killer T cells and their functions in atherosclerosis and obesity: a therapeutic perspective for cardiovascular diseases. (Masters Thesis). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/301208
Chicago Manual of Style (16th Edition):
Vrugt, A M van de. “Natural Killer T cells and their functions in atherosclerosis and obesity: a therapeutic perspective for cardiovascular diseases.” 2014. Masters Thesis, Universiteit Utrecht. Accessed April 17, 2021.
http://dspace.library.uu.nl:8080/handle/1874/301208.
MLA Handbook (7th Edition):
Vrugt, A M van de. “Natural Killer T cells and their functions in atherosclerosis and obesity: a therapeutic perspective for cardiovascular diseases.” 2014. Web. 17 Apr 2021.
Vancouver:
Vrugt AMvd. Natural Killer T cells and their functions in atherosclerosis and obesity: a therapeutic perspective for cardiovascular diseases. [Internet] [Masters thesis]. Universiteit Utrecht; 2014. [cited 2021 Apr 17].
Available from: http://dspace.library.uu.nl:8080/handle/1874/301208.
Council of Science Editors:
Vrugt AMvd. Natural Killer T cells and their functions in atherosclerosis and obesity: a therapeutic perspective for cardiovascular diseases. [Masters Thesis]. Universiteit Utrecht; 2014. Available from: http://dspace.library.uu.nl:8080/handle/1874/301208
Vanderbilt University
4.
Braun, Nicole Ann.
Effects of Dyslipidemia on Invariant Natural Killer T Cell Activation.
Degree: PhD, Pathology, 2011, Vanderbilt University
URL: http://hdl.handle.net/1803/11285
► Invariant natural killer T (iNKT) cells are a specialized subset of immune regulatory cells that recognize glycolipid antigens and are thought to be pro-atherogenic under…
(more)
▼ Invariant natural killer T (iNKT)
cells are a specialized subset of immune regulatory
cells that recognize glycolipid antigens and are thought to be pro-atherogenic under hyperlipidemic conditions. We previously reported that hyperlipidemic apolipoprotein E-deficient (apoE-/-) mice have decreased iNKT cell-mediated cytokine production in vitro and in vivo in response to alpha-galactosylceramide (a-GalCer), a prototypic iNKT cell glycolipid antigen. These data suggested changes in endogenous circulating lipids can affect normal iNKT cell functions. In the current study, we investigated whether dyslipidemia-associated perturbed iNKT cell function is due to intrinsic changes in iNKT
cells or defects in the ability of antigen presenting
cells to activate iNKT
cells. Our data reveal that iNKT
cells from dyslipidemic apoE-/- mice exhibit a phenotype similar to those rendered anergic due to chronic stimulation. We also tested the ability of B6 and apoE-/- splenic dendritic
cells (DCs) to present a-GalCer to purified iNKT
cells. Although DCs from apoE-/- mice were able to activate B6 iNKT
cells, iNKT
cells from apoE-/- mice were not able to respond to B6 DCs. These data suggest that chronic hyperlipidemia induces an iNKT cell phenotype that is unresponsive to further simulation by exogenous glycolipid, and that sustained unresponsiveness appears to be iNKT cell intrinsic. Additionally, our results indicate that increased circulating lipids exert direct effects upon iNKT
cells which lead to decreased responsiveness.
Advisors/Committee Members: Luc van Kaer (committee member), Anne Kenworthy (committee member), Gregory Sephel (committee member), Larry Swift (committee member), Jay Jerome (Committee Chair).
Subjects/Keywords: lipids; NKT cells; apolipoprotein E; atherosclerosis; immunity
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APA ·
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APA (6th Edition):
Braun, N. A. (2011). Effects of Dyslipidemia on Invariant Natural Killer T Cell Activation. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/11285
Chicago Manual of Style (16th Edition):
Braun, Nicole Ann. “Effects of Dyslipidemia on Invariant Natural Killer T Cell Activation.” 2011. Doctoral Dissertation, Vanderbilt University. Accessed April 17, 2021.
http://hdl.handle.net/1803/11285.
MLA Handbook (7th Edition):
Braun, Nicole Ann. “Effects of Dyslipidemia on Invariant Natural Killer T Cell Activation.” 2011. Web. 17 Apr 2021.
Vancouver:
Braun NA. Effects of Dyslipidemia on Invariant Natural Killer T Cell Activation. [Internet] [Doctoral dissertation]. Vanderbilt University; 2011. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/1803/11285.
Council of Science Editors:
Braun NA. Effects of Dyslipidemia on Invariant Natural Killer T Cell Activation. [Doctoral Dissertation]. Vanderbilt University; 2011. Available from: http://hdl.handle.net/1803/11285
Brigham Young University
5.
Liu, Yang.
Synthesis of Glycolipids and Evaluation of Their NKT Cell Stimulatory Properties.
Degree: PhD, 2010, Brigham Young University
URL: https://scholarsarchive.byu.edu/cgi/viewcontent.cgi?article=3292&context=etd
► Natural killer T (NKT) cells are a subset of T cells that modify a variety of immune responses. NKT cells recognize glycolipid antigen presented…
(more)
▼ Natural killer T (NKT) cells are a subset of T cells that modify a variety of immune responses. NKT cells recognize glycolipid antigen presented by a molecule called CD1d, a nonclassical antigen-presenting molecule. The best known subset of CD1d-dependent NKT cells expresses an invariant T cell receptor Vα (TCR-α) chain. These are referred to as type I or invariant NKT (iNKT) cells. When stimulated by a glycolipid, NKT cells rapidly release large amounts of cytokines. Cytokines released by NKT cells can induce either Th1 or Th2 responses. Th1 cytokines are effective in regulating bacterial, parasitic, and viral infections. But Th1 responses are also involved in some autoimmune diseases, such as type 1 diabetes, lupus, rheumatoid arthritis, and allergen-induced asthma. Th2 cytokines can attenuate proinflammatory Th1 responses and therefore prevent some autoimmune diseases. Lysosomal processing and CD1d loading is very important in regulating the stimulatory properties of antigens. Analogs of KRN7000, with small molecules appended on C6” position of the galactose portion, do not significantly change stimulation of NKT cells. The question is if the substitution at this position would influence the lysosomal processing. Two sets of mono- and disaccharides with and without substitution at C6” position were prepared and evaluated the NKT cell stimulatory properties. The substitution at the C6” position of the sugar moiety of glycolipids do not significantly impact the stimulatory properties of glycolipids and their processing in lysosome. Small changes at C6” are well tolerated. A double bond in the acyl chain and modification of the C6” functional group helped the glycolipid loading into CD1d and NKT cells stimulation. PBS57 is 100 times more active than KRN 7000 in stimulation of NKT cells responses in vitro and in vivo. This improvement is probably due to increasing solubility and improving binding ability with the CD1d.
Subjects/Keywords: NKT cells; CD1d; Glycolipid; Biochemistry; Chemistry
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APA ·
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APA (6th Edition):
Liu, Y. (2010). Synthesis of Glycolipids and Evaluation of Their NKT Cell Stimulatory Properties. (Doctoral Dissertation). Brigham Young University. Retrieved from https://scholarsarchive.byu.edu/cgi/viewcontent.cgi?article=3292&context=etd
Chicago Manual of Style (16th Edition):
Liu, Yang. “Synthesis of Glycolipids and Evaluation of Their NKT Cell Stimulatory Properties.” 2010. Doctoral Dissertation, Brigham Young University. Accessed April 17, 2021.
https://scholarsarchive.byu.edu/cgi/viewcontent.cgi?article=3292&context=etd.
MLA Handbook (7th Edition):
Liu, Yang. “Synthesis of Glycolipids and Evaluation of Their NKT Cell Stimulatory Properties.” 2010. Web. 17 Apr 2021.
Vancouver:
Liu Y. Synthesis of Glycolipids and Evaluation of Their NKT Cell Stimulatory Properties. [Internet] [Doctoral dissertation]. Brigham Young University; 2010. [cited 2021 Apr 17].
Available from: https://scholarsarchive.byu.edu/cgi/viewcontent.cgi?article=3292&context=etd.
Council of Science Editors:
Liu Y. Synthesis of Glycolipids and Evaluation of Their NKT Cell Stimulatory Properties. [Doctoral Dissertation]. Brigham Young University; 2010. Available from: https://scholarsarchive.byu.edu/cgi/viewcontent.cgi?article=3292&context=etd
University of Melbourne
6.
PELLICCI, DANIEL GRANT.
The molecular and structural basis for antigen recognition by NKT cells.
Degree: 2012, University of Melbourne
URL: http://hdl.handle.net/11343/38046
► NKT cells are a subset of T lymphocytes that influence a large array of immune responses ranging from cancer to autoimmune disease. The involvement of…
(more)
▼ NKT cells are a subset of T lymphocytes that influence a large array of immune responses ranging from cancer to autoimmune disease. The involvement of NKT cells in these immune responses is primarily due to their ability to rapidly produce immunoregulatory cytokines in response to glycolipid antigens presented by the antigen presentation molecule, CD1d. Understanding the precise molecular interactions that govern NKT cell recognition of glycolipid antigens will provide important insight into how these cells can be manipulated in a therapeutic setting.
NKT cells express a semi-invariant T cell receptor (TCR), Vα24-Jα18 in humans, Vα14-Jα18 in mice; Vβ11 in humans, Vβ8, Vβ7 or Vβ2 in mice. The restricted T cell repertoire of NKT cells is thought to reflect their unusual antigen specificity, as most other T cell populations recognise peptide antigens presented by major histocompatibility complexes (MHC). Although NKT express a restricted T cell repertoire due to limited TCR chain usage, it is important to note that the complementarity determining regions (CDR) of the TCR β-chain and more specifically, CDR3β, can be enormously diverse. This thesis provides important insight into how NKT TCR diversity is critical for the recognition of functionally distinct glycolipid antigens.
Structural analysis of the first human NKT TCR in complex with hCD1d loaded with the foreign glycolipid antigen, α-galactosylceramide (α-GalCer) revealed a strikingly different docking mode compared to that observed for TCR/MHC-peptide complexes. In contrast to a diagonal docking mode that is common for peptide recognition, the NKT TCR docked parallel to, and at the far end of CD1d binding cleft allowing the highly conserved invariant α-chain to dominate interactions with CD1d/α-GalCer. Given that the three β-chains expressed by mouse NKT cells exhibit non-conserved differences in the proposed CD1d docking regions, it was important to establish how these TCRs contributed to glycolipid recognition. The structures of the three main mouse NKT TCRs in complex with mouse CD1d loaded with α-GalCer were solved, revealing, that while the docking mode is broadly similar for each TCR, clear differences in the contribution of each TCR β-chain were observed. Furthermore, a comparison of mouse NKT TCRs using retroviral NKT cell lines, fresh thymic NKT cells and soluble NKT TCRs revealed that even minor alterations in glycolipids could lead to drastic alterations in cellular responses and affinity. Collectively, these studies demonstrate that different TCR β-chains provide an altered landscape that can influence interactions with structurally distinct glycolipid antigens.
Whilst considerable effort has been made in understanding how NKT cells recognise foreign α-linked antigens, it is still unclear how NKT cells are involved in a range of immune responses such as cancer, autoimmunity, infection and inflammation. In these…
Subjects/Keywords: NKT cells; glycolipids; T-cell receptor
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APA (6th Edition):
PELLICCI, D. G. (2012). The molecular and structural basis for antigen recognition by NKT cells. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/38046
Chicago Manual of Style (16th Edition):
PELLICCI, DANIEL GRANT. “The molecular and structural basis for antigen recognition by NKT cells.” 2012. Doctoral Dissertation, University of Melbourne. Accessed April 17, 2021.
http://hdl.handle.net/11343/38046.
MLA Handbook (7th Edition):
PELLICCI, DANIEL GRANT. “The molecular and structural basis for antigen recognition by NKT cells.” 2012. Web. 17 Apr 2021.
Vancouver:
PELLICCI DG. The molecular and structural basis for antigen recognition by NKT cells. [Internet] [Doctoral dissertation]. University of Melbourne; 2012. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/11343/38046.
Council of Science Editors:
PELLICCI DG. The molecular and structural basis for antigen recognition by NKT cells. [Doctoral Dissertation]. University of Melbourne; 2012. Available from: http://hdl.handle.net/11343/38046
Universitat Autònoma de Barcelona
7.
Escribà Garcia, Laura.
Cellular immunotherapy for B-cell lymphoma with B-cell lymphoma with NKT-cell agonists.
Degree: Departament de Bioquímica i Biologia Molecular, 2016, Universitat Autònoma de Barcelona
URL: http://hdl.handle.net/10803/386489
► Natural killer T (NKT) cells are a small population of lymphocytes with unique specificity for glycolipid antigens presented by non-polymorphic CD1d receptor on APC, mainly…
(more)
▼ Natural killer T (
NKT)
cells are a small population of lymphocytes with unique specificity for glycolipid antigens presented by non-polymorphic CD1d receptor on APC, mainly presented on dendritic
cells (DCs).
NKT cells play a central role in tumor immunology since they coordinate innate and adaptive immune responses. These
cells can be activated with the prototypic lipid α-galactosylceramide (α-GalCer), stimulating IFN-γ production and cytokine secretion (eg, IL-12, IL-4, IL-17) that contribute to the enhancement of DC function and the induction of NK, B and T-cell activation. We evaluated the antitumor effect of a combination of DCs and irradiated tumor
cells with the
NKT cell agonist α-GalCer in a mouse model of B-cell lymphoma.
The therapeutic vaccine consisting of DCs, tumor
cells and α-GalCer was able to eradicate B-cell lymphoma in all treated mice, and was superior to any vaccine combination, including α-GalCer alone, irradiated tumor
cells with DCs, and DCs with α-GalCer. Importantly, treated mice with the vaccine were resistant to a tumor rechallenge, suggesting the development of a memory immune response. In addition, the immune response was tumor-specific since all the mice were unable to reject a syngeneic A20 B-cell lymphoma. In addition to in vivo evaluation of the therapeutic vaccine, the cytokine profile induced by the treatment was evaluated, showing a combination of Th1 and Th2 cytokines together with IL-17. When we looked at effector
cells, we observed that the vaccine induces a high
NKT and NK-cell expansion, as well as a high increase of IFN-γ secreting
NKT, NK and tumor-specific T
cells. NK
cells played a critical role in the antitumor effect observed after the therapeutic treatment and there was also an activation of B
cells since IgG antibodies against tumor
cells were found in treated mice.
The therapeutic vaccine consisting of dendritic
cells, tumor
cells and α-GalCer efficiently eradicates B-cell lymphoma in a therapeutic setting. This immune response is long-lasting, tumor-specific, and it is associated with an expansion of NK and
NKT cells, an increase of IFN-γ secreting NK,
NKT and T
cells and B-cell activation.
Advisors/Committee Members: [email protected] (authoremail), true (authoremailshow), Briones Meijide, Javier (director), Bosch Merino, Assumpció (tutor), true (authorsendemail).
Subjects/Keywords: Limfoma B; Linfoma B; B-cell lymphoma; Cèl.lules NKT; Células NKT; NKT cells; Immunoteràpia; Inmunoterapia; Immunotherapy; Ciències Experimentals; 6
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APA ·
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APA (6th Edition):
Escribà Garcia, L. (2016). Cellular immunotherapy for B-cell lymphoma with B-cell lymphoma with NKT-cell agonists. (Thesis). Universitat Autònoma de Barcelona. Retrieved from http://hdl.handle.net/10803/386489
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Escribà Garcia, Laura. “Cellular immunotherapy for B-cell lymphoma with B-cell lymphoma with NKT-cell agonists.” 2016. Thesis, Universitat Autònoma de Barcelona. Accessed April 17, 2021.
http://hdl.handle.net/10803/386489.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Escribà Garcia, Laura. “Cellular immunotherapy for B-cell lymphoma with B-cell lymphoma with NKT-cell agonists.” 2016. Web. 17 Apr 2021.
Vancouver:
Escribà Garcia L. Cellular immunotherapy for B-cell lymphoma with B-cell lymphoma with NKT-cell agonists. [Internet] [Thesis]. Universitat Autònoma de Barcelona; 2016. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/10803/386489.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Escribà Garcia L. Cellular immunotherapy for B-cell lymphoma with B-cell lymphoma with NKT-cell agonists. [Thesis]. Universitat Autònoma de Barcelona; 2016. Available from: http://hdl.handle.net/10803/386489
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
8.
Cristhiane Favero de Aguiar.
Papel das células NKT na homeostase e inflamação intestinal.
Degree: 2017, University of São Paulo
URL: http://www.teses.usp.br/teses/disponiveis/42/42133/tde-12072017-112312/
► As células NKT compreendem um grupo distinto de linfócitos caracterizados pela reatividade a glicolipídios apresentados pela molécula CD1d. Em nosso trabalho, nós investigamos a participação…
(more)
▼ As células NKT compreendem um grupo distinto de linfócitos caracterizados pela reatividade a glicolipídios apresentados pela molécula CD1d. Em nosso trabalho, nós investigamos a participação das células NKT na homeostase intestinal utilizando animais nocautes para essas células e também caracterizamos os subtipos de NKT no intestino. Nos animais nocautes observamos que a ausência de células NKT influencia a microbiota e a homeostase intestinal. Os animais nocautes possuem diminuição no filo Firmicutes, diminuição dos níveis de IgA nas fezes e de TGF-β no intestino. Esses animais também são mais suscetíveis à colite induzida por DSS, apresentando menor sobrevida, menor tamanho do cólon e aumento no score. Nos animais selvagens, a indução do subtipo NKT10 diminuiu a inflamação intestinal, não causou intensa redução do cólon e reduziu a frequência de células NKT e do subtipo NKT17 no intestino. Nossos resultados indicam que as células NKT
intestinais são peças importantes para a homeostase intestinal e para a composição da microbiota intestinal.
NKT cells comprise a distinct group of lymphocytes characterized by their reactivity to glycolipids presented by CD1d. In our work, we investigated the involvement of NKT cells in intestinal homeostasis using knockout (KO) mice and we also characterized NKT subtypes in the intestine. The absence of NKT cells in KO mice influenced the intestinal microbiota and homeostasis. KO mice had a decrease in the Firmicutes phyla, in the levels of fecal IgA and TGF-β in the intestine. These mice are also more susceptible to DSS-induced colitis, exhibiting worse survival, severe shortening of the colon and higher score. In wild type mice, the induction of the NKT10 subtype decreased intestinal inflammation, did not cause intense reduction of colon and reduced the frequency of NKT cells and the NKT17 subtype in the intestine. Our results indicate that intestinal NKT cells are
important for intestinal homeostasis and microbiota composition.
Advisors/Committee Members: Niels Olsen Saraiva Câmara, José Antonio Tavares de Albuquerque, Alexandre de Castro Keller, Eliana Faquim de Lima Mauro, Pedro Manoel Mendes de Moraes Vieira.
Subjects/Keywords: Células NKT; Colite; Inflamação; Intestino; Microbiota; Colitis; Inflammation; Intestine; Microbiota; NKT cells
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APA (6th Edition):
Aguiar, C. F. d. (2017). Papel das células NKT na homeostase e inflamação intestinal. (Doctoral Dissertation). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/42/42133/tde-12072017-112312/
Chicago Manual of Style (16th Edition):
Aguiar, Cristhiane Favero de. “Papel das células NKT na homeostase e inflamação intestinal.” 2017. Doctoral Dissertation, University of São Paulo. Accessed April 17, 2021.
http://www.teses.usp.br/teses/disponiveis/42/42133/tde-12072017-112312/.
MLA Handbook (7th Edition):
Aguiar, Cristhiane Favero de. “Papel das células NKT na homeostase e inflamação intestinal.” 2017. Web. 17 Apr 2021.
Vancouver:
Aguiar CFd. Papel das células NKT na homeostase e inflamação intestinal. [Internet] [Doctoral dissertation]. University of São Paulo; 2017. [cited 2021 Apr 17].
Available from: http://www.teses.usp.br/teses/disponiveis/42/42133/tde-12072017-112312/.
Council of Science Editors:
Aguiar CFd. Papel das células NKT na homeostase e inflamação intestinal. [Doctoral Dissertation]. University of São Paulo; 2017. Available from: http://www.teses.usp.br/teses/disponiveis/42/42133/tde-12072017-112312/
9.
Felipe Grabarz.
Células NKT, macrófagos M2 e o desenvolvimento da fibrose pulmonar.
Degree: 2014, University of São Paulo
URL: http://www.teses.usp.br/teses/disponiveis/42/42133/tde-20022015-171616/
► A fibrose pulmonar é uma via comum de várias doenças agudas e crônicas do interstício pulmonar que pode resultar na cicatrização anormal do pulmão. Há…
(more)
▼ A fibrose pulmonar é uma via comum de várias doenças agudas e crônicas do interstício pulmonar que pode resultar na cicatrização anormal do pulmão. Há acúmulo excessivo das proteínas da matriz extracelular levando a desestruturação das paredes alveolares, e consequente perda das trocas gasosas pelos pulmões. As células NKT são grande fonte de citocinas e podem ser cruciais na polarização de macrófagos para o fenótipo M2. O projeto tem a hipótese de que as células NKT podem influenciar o desenvolvimento da fibrose pulmonar via modulação de macrófagos. Para isso, animais selvagens e knockout para células NKT invariante (Ja18-/-) foram submetidos ao protocolo de indução de fibrose pulmonar pela bleomicina. Os resultados indicam que o grupo Ja18-/- assim como os grupos experimentais que receberam agonistas para células NKT apresentaram uma proteção contra a fibrose pulmonar uma vez que houve menor síntese de hidroxiprolina, deposição de colágeno,
citocinas pró-fibróticas e a manutenção de macrófagos M1 no tecido pulmonar.
Pulmonary fibrosis is a common pathway of various acute and chronic interstitial lung diseases that may result in abnormal healing of the lung. There is excessive accumulation of extracellular matrix proteins, leading to disruption of the alveolar walls and the consequent loss of gas exchange through the lungs. NKT cells are a big source of cytokines and may be crucial in the polarization of macrophages to the M2 phenotype. This project has hypothesized that NKT cells can influence the development of pulmonary fibrosis through modulation of macrophages. For this, wild and knockout invariant NKT cells (Ja18-/-) mice were subjected to the protocol of bleomycin induced pulmonary fibrosis. The results indicate that the group Ja18-/- as well as the experimental groups receiving agonists for NKT cells showed protection against lung fibrosis since there was less synthesis of hydroxyproline, collagen
deposition, pro-fibrotic cytokines and maintenance of macrophages M1 in lung tissue.
Advisors/Committee Members: Niels Olsen Saraiva Câmara, Jacqueline de Fátima Jacysyn, Alexandre Lourenço.
Subjects/Keywords: Bleomicina; Células NKT; Fibrose pulmonar; Macrófagos M2; Bleomycin; Lung fibrosis; M2 macrophages; NKT cells
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MLA ·
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APA (6th Edition):
Grabarz, F. (2014). Células NKT, macrófagos M2 e o desenvolvimento da fibrose pulmonar. (Masters Thesis). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/42/42133/tde-20022015-171616/
Chicago Manual of Style (16th Edition):
Grabarz, Felipe. “Células NKT, macrófagos M2 e o desenvolvimento da fibrose pulmonar.” 2014. Masters Thesis, University of São Paulo. Accessed April 17, 2021.
http://www.teses.usp.br/teses/disponiveis/42/42133/tde-20022015-171616/.
MLA Handbook (7th Edition):
Grabarz, Felipe. “Células NKT, macrófagos M2 e o desenvolvimento da fibrose pulmonar.” 2014. Web. 17 Apr 2021.
Vancouver:
Grabarz F. Células NKT, macrófagos M2 e o desenvolvimento da fibrose pulmonar. [Internet] [Masters thesis]. University of São Paulo; 2014. [cited 2021 Apr 17].
Available from: http://www.teses.usp.br/teses/disponiveis/42/42133/tde-20022015-171616/.
Council of Science Editors:
Grabarz F. Células NKT, macrófagos M2 e o desenvolvimento da fibrose pulmonar. [Masters Thesis]. University of São Paulo; 2014. Available from: http://www.teses.usp.br/teses/disponiveis/42/42133/tde-20022015-171616/
Vanderbilt University
10.
Covarrubias, Roman.
The Role of Macrophage Low Density Lipoprotein Receptor-Related Protein in the Activation of Invariant Natural Killer T cells.
Degree: PhD, Pathology, 2015, Vanderbilt University
URL: http://hdl.handle.net/1803/11158
► Invariant natural killer T (iNKT) cells are unique group of lymphocytes that secrete copious amounts of immunoregulatory cytokines upon activation. This allows iNKT cells to…
(more)
▼ Invariant natural killer T (iNKT)
cells are unique group of lymphocytes that secrete copious amounts of immunoregulatory cytokines upon activation. This allows iNKT
cells to modulate a wide range of mouse models that model human disorders such as multiple sclerosis, metastatic cancer, atherosclerosis, etc. The activation of iNKT
cells relies on the presentation of glycolipids in the context of major histocompatibility molecule CD1d on antigen presenting
cells (APCs). The mechanisms and cellular factors involved in the preparation of glycolipids for iNKT cell activation remain to be defined, yet expression of molecules involved in lipoprotein metabolism have been shown to play a role in iNKT cell activation. In the current study, we investigated the expression of low density lipoprotein receptor-related protein (LRP) and determined that macrophages (MFs) are the main cell type expressing LRP. Using a mouse model with a genetic deletion of LRP in MFs, we demonstrated that in vivo activation of iNKT
cells with prototypical iNKT ligand, a-galactosyl-ceramide (aGC), leads to decreased serum levels of interleukin-4 (IL-4) and decreased production of IL-4 by iNKT
cells. Using a fluorescently labeled glycolipid we show that LRP deletion increases the rate of glycolipid flux and through generation of bone marrow chimaeras determined that the decrease of the IL-4 response is iNKT cell extrinsic. Additionally, our studies revealed that in WT mice, challenge with aGC leads to a decrease in LRP levels that is iNKT cell and interferon-gamma dependent. These data demonstrate that LRP expression in MFs is critical for the activation of iNKT
cells and that iNKT cell derived interferon-gamma can modulate LRP expression in WT MFs.
Advisors/Committee Members: Luc Van kaer (committee member), Adam Seegmiller (committee member), Sergio Fazio (committee member), Tom Aune (committee member), Virginia Shepherd (Committee Chair).
Subjects/Keywords: NKT cells; immune regulation; LRP; LDL receptor; apolipoprotein; glycolipids
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APA ·
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MLA ·
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Manager
APA (6th Edition):
Covarrubias, R. (2015). The Role of Macrophage Low Density Lipoprotein Receptor-Related Protein in the Activation of Invariant Natural Killer T cells. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/11158
Chicago Manual of Style (16th Edition):
Covarrubias, Roman. “The Role of Macrophage Low Density Lipoprotein Receptor-Related Protein in the Activation of Invariant Natural Killer T cells.” 2015. Doctoral Dissertation, Vanderbilt University. Accessed April 17, 2021.
http://hdl.handle.net/1803/11158.
MLA Handbook (7th Edition):
Covarrubias, Roman. “The Role of Macrophage Low Density Lipoprotein Receptor-Related Protein in the Activation of Invariant Natural Killer T cells.” 2015. Web. 17 Apr 2021.
Vancouver:
Covarrubias R. The Role of Macrophage Low Density Lipoprotein Receptor-Related Protein in the Activation of Invariant Natural Killer T cells. [Internet] [Doctoral dissertation]. Vanderbilt University; 2015. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/1803/11158.
Council of Science Editors:
Covarrubias R. The Role of Macrophage Low Density Lipoprotein Receptor-Related Protein in the Activation of Invariant Natural Killer T cells. [Doctoral Dissertation]. Vanderbilt University; 2015. Available from: http://hdl.handle.net/1803/11158
Penn State University
11.
Zhao, Jun.
Regulatory role of NKT cells on effects of 1,25(OH)2D3 in mice with EAE.
Degree: 2012, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/15368
► min D is an immune regulator and has been shown to be involved in the development and treatment of autoimmune diseases such as multiple sclerosis…
(more)
▼ min D is an immune regulator and has been shown to be involved in the
development and treatment of autoimmune diseases such as multiple sclerosis (MS). The
active form of vitamin D, 1,25(OH)2D3, has been shown to suppress experimental
autoimmune encephalomyelitis (EAE). Invariant Natural Kill T (iNKT)
cells have been
proven to be an important suppressor of EAE. The development of iNKT
cells was
impaired due to vitamin D and or vitamin D receptor (VDR) deficiency. 1,25(OH)2D3
had less effects in protecting CD1d knockout (KO) mice from EAE than in WT. CD1d
KO mice with 1,25(OH)2D3 supplementation had significantly higher incidence of EAE
and developed significantly higher EAE scores than WT mice with 1,25(OH)2D3
treatment. 1,25(OH)2D3 was also less effective in preventing Jα18 KO mice against EAE
than in WT. Jα18 KO mice on 1,25(OH)2D3 treatment had significantly higher incidence
of EAE and significantly higher cumulative EAE scores than WT mice with 1,25(OH)2D3
treatment. Either 1,25(OH)2D3 treatment or alpha-galactosylceramide (alpha-GalCer)
administration failed to prevent EAE development in Interleukin-4 (IL-4) KO mice.
These data suggests that the protective effects of 1,25(OH)2D3 against EAE might be
regulated by iNKT
cells and IL-4 might be a positive regulator in the beneficial effects of
either 1,25(OH)2D3 or alpha-GalCer on EAE inhibition.
Advisors/Committee Members: Margherita Teresa Anna Cantorna, Thesis Advisor/Co-Advisor.
Subjects/Keywords: 1; 25(OH)2D3; EAE; NKT cells; IL-4
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CSE |
Export
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Manager
APA (6th Edition):
Zhao, J. (2012). Regulatory role of NKT cells on effects of 1,25(OH)2D3 in mice with EAE. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/15368
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Zhao, Jun. “Regulatory role of NKT cells on effects of 1,25(OH)2D3 in mice with EAE.” 2012. Thesis, Penn State University. Accessed April 17, 2021.
https://submit-etda.libraries.psu.edu/catalog/15368.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Zhao, Jun. “Regulatory role of NKT cells on effects of 1,25(OH)2D3 in mice with EAE.” 2012. Web. 17 Apr 2021.
Vancouver:
Zhao J. Regulatory role of NKT cells on effects of 1,25(OH)2D3 in mice with EAE. [Internet] [Thesis]. Penn State University; 2012. [cited 2021 Apr 17].
Available from: https://submit-etda.libraries.psu.edu/catalog/15368.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Zhao J. Regulatory role of NKT cells on effects of 1,25(OH)2D3 in mice with EAE. [Thesis]. Penn State University; 2012. Available from: https://submit-etda.libraries.psu.edu/catalog/15368
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Manchester
12.
Gieschen-Krische, Mary.
The role of NKT cells following solid organ
transplantation.
Degree: 2014, University of Manchester
URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:242866
► Introduction: NKT cells are categorised as borderline between NK and T cells, sharing phenotypic and functional characteristics of both cells, demonstrating their capacity to contritube…
(more)
▼ Introduction:
NKT cells are categorised as
borderline between NK and T
cells, sharing phenotypic and
functional characteristics of both
cells, demonstrating their
capacity to contritube to both pro- or anti-inflammatory processes.
However, the role of these
cells among lung transplant recipients
remains largely unknown. The aim of this study was to determine the
role of
NKT cells following lung transplantation. Methods:
NKT
cells were quantified and characterised according to markers of:
activation (CD107a, CD161, NKG2D) and immunomodulation (CD200 and
CD200R) in peripheral blood and BALs.
NKT cell numbers and
phenotypes were correlated to clinical variables:
immunosuppression, acute rejection, acute infections (viral,
bacterial and fungal), bronchiolitis obliterans syndrome (BOS
grade), lung function, and demographic variables. Interactions
between
NKT cells and the transplanted lung were linked by
determining the relative expression of immunomodulatory ligand
CD200 in lung biopsies. In vitro models were employed to determine
the role of
NKT cells to acute lung injury, either alone or in
combination with
cells of the mononuclear phagocyte system (MPS).
Results: Higher numbers of immunomodulatory
NKT cells (CD200+ and
CD200R+) were found as lung function decreased. Data from
peripheral blood indicates that recipients whose donors or
themselves had been exposed to CMV infection demonstrated increased
numbers of
NKT cells. Patients with active EBV infections
demonstrated higher
NKT cell numbers expressing CD200 and CD200R.
Data from BALs, indicates that patients with active fungal
infections present higher immunomodulatory (CD200R)
NKT cells and
lower cytotoxicity marker (CD107a). In peripheral blood, lung
recipients demonstrated higher
NKT cell numbers compared to healthy
volunteers. However, the lower relative mean expression of
functional markers in the lung transplant group suggests that
cells
are less active. In vitro cultures with immunosuppressants
demonstrated that cell cycle inhibitors (MMF and AZA) and
corticosteroids (Prednisolone) are likely to inhibit
NKT cell
proliferation, while calcineurin inhibitors (Cyclosporine A and
Tacrolimus) decrease the relative mean expression of activation
markers. Clinical observations indicate that higher doses of
Azathioprine may correlate with increased
NKT cell numbers and the
relative expression of CD200 and CD200R. However, under these
conditions the relative expression of activation marker NKG2D
decreases. In vitro data from the acute injury model indicates that
NKT cells are capable to migrate into the injured lung and become
activated following transmigration which is facilitated by the
presence of monocytes. We also observed the interaction of
NKT
cells with endothelial
cells, monocytes and macrophages. Also, the
relative mean expression of CD200 and CD200R increased at the
capillary layer, regardless of injury while upregulation of
activation markers (CD107a, CD161 and NKG2D) was found at the
capillary layer, following injury. In contrast, the alveolar layer…
Advisors/Committee Members: FILDES, JAMES J, Fildes, James, Yonan, Nizar.
Subjects/Keywords: NKT cells; lung; transplantation; immunosuppression; acute lung injury
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MLA ·
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Export
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Manager
APA (6th Edition):
Gieschen-Krische, M. (2014). The role of NKT cells following solid organ
transplantation. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:242866
Chicago Manual of Style (16th Edition):
Gieschen-Krische, Mary. “The role of NKT cells following solid organ
transplantation.” 2014. Doctoral Dissertation, University of Manchester. Accessed April 17, 2021.
http://www.manchester.ac.uk/escholar/uk-ac-man-scw:242866.
MLA Handbook (7th Edition):
Gieschen-Krische, Mary. “The role of NKT cells following solid organ
transplantation.” 2014. Web. 17 Apr 2021.
Vancouver:
Gieschen-Krische M. The role of NKT cells following solid organ
transplantation. [Internet] [Doctoral dissertation]. University of Manchester; 2014. [cited 2021 Apr 17].
Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:242866.
Council of Science Editors:
Gieschen-Krische M. The role of NKT cells following solid organ
transplantation. [Doctoral Dissertation]. University of Manchester; 2014. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:242866
13.
MELO RODRIGUEZ, ASHANTY MAGGVIE.
The role and treatment potential of natural killer T (NKT) cells in patients with upper gastrointestinal cancers.
Degree: School of Medicine. Discipline of Immunology, 2019, Trinity College Dublin
URL: http://hdl.handle.net/2262/90022
► Oesophageal adenocarcinoma (OAC), squamous cell carcinoma (SSC) and gastric cancers (GAC), collectively cause over 1.3 million deaths worldwide reported in 2018. Current therapeutic regimens focus…
(more)
▼ Oesophageal adenocarcinoma (OAC), squamous cell carcinoma (SSC) and gastric cancers (GAC), collectively cause over 1.3 million deaths worldwide reported in 2018. Current therapeutic regimens focus on chemo-radiotherapy prior to surgery, however, only 20-30% of patients respond to treatment. Therefore, new treatments are urgently required. Invariant natural killer T (iNKT)
cells are innate T
cells with semi-invariant T cell receptors that recognise glycolipids presented by CD1d. iNKT
cells have antitumour activities that are currently being tested as cellular therapies iNKT cell frequencies were quantified in pre- and post-treatment blood and omentum from 152 patients with GAC, SCC or OAC by flow cytometry. They were found to be depleted in peripheral blood from GAC, SCC and OAC patients compared to controls. Omentum had higher frequencies of iNKT
cells in the cancer patients compared to blood. These findings suggest that iNKT
cells may mediate immunity against GAC, SSC and OAC and that the omentum could be a source of
cells for use in adoptive cell therapy. Since clinical trials involving iNKT
cells in other cancers have to date shown limited clinical efficacy, we investigated if the antitumour activities of these
cells could be improved by coordinating treatment with current chemotherapy and radiotherapy regimens or by the use of alternative glycolipid ligands. iNKT
cells were isolated from healthy donor blood samples and expanded in vitro. They were treated with various concentrations of cisplatin, carboplatin, paclitaxel, 5-fluorouracil for 24 or 48h or irradiated with a single dose of 2 Gy or 10 Gy or five fractionated doses of 2 Gy.
Cells were then assayed for viability, apoptotic markers, or co-cultured with CD1d transfected HeLa
cells pulsed with the iNKT cell agonist ligand, ?-galactosylceramide (?-GalCer), for assays of cytolytic degranulation and intracellular cytokine, granzyme B and perforin production. Cisplatin, 5-FU, carboplatin, paclitaxel and radiation exhibited a dose-dependent inhibition of iNKT cell viability. Cisplatin also inhibited degranulation and IFN-?, but not IL-4, production by viable iNKT
cells. While 5-FU, carboplatin, paclitaxel and radiation increased apoptosis of iNKT
cells, it did not affect activation. A number of synthetic glycolipids analogues of ?-GalCer were also tested for their ability to bind to CD1d-transfected HeLa
cells and activate the antitumour activities of iNKT
cells. One novel glycolipid, XZ7, induced cytolytic degranulation and IFN-? production by CD8+ and double negative iNKT
cells, suggesting that it may be superior to ?-GalCer as a lead compound for activating the antitumour activities of iNKT
cells. We also tested for the presence of non-invariant (type II)
NKT cells reactive against a number of glycolipids that were previously shown to bind to CD1d and stimulate T
cells, in OAC patients and control subjects. OAC patients had higher frequencies of sulfatide and tetramyristoyl-cardiolipin (TO CL)-specific T
cells compared to controls. Most of these
cells…
Advisors/Committee Members: Doherty, Derek, Lysaght, Joanne.
Subjects/Keywords: Oesophageal cancer; Gastric cancer; NKT cells; Glycolipids; Radiotherapy; Chemotherapy; CD1d
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MLA ·
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CSE |
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Manager
APA (6th Edition):
MELO RODRIGUEZ, A. M. (2019). The role and treatment potential of natural killer T (NKT) cells in patients with upper gastrointestinal cancers. (Thesis). Trinity College Dublin. Retrieved from http://hdl.handle.net/2262/90022
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
MELO RODRIGUEZ, ASHANTY MAGGVIE. “The role and treatment potential of natural killer T (NKT) cells in patients with upper gastrointestinal cancers.” 2019. Thesis, Trinity College Dublin. Accessed April 17, 2021.
http://hdl.handle.net/2262/90022.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
MELO RODRIGUEZ, ASHANTY MAGGVIE. “The role and treatment potential of natural killer T (NKT) cells in patients with upper gastrointestinal cancers.” 2019. Web. 17 Apr 2021.
Vancouver:
MELO RODRIGUEZ AM. The role and treatment potential of natural killer T (NKT) cells in patients with upper gastrointestinal cancers. [Internet] [Thesis]. Trinity College Dublin; 2019. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/2262/90022.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
MELO RODRIGUEZ AM. The role and treatment potential of natural killer T (NKT) cells in patients with upper gastrointestinal cancers. [Thesis]. Trinity College Dublin; 2019. Available from: http://hdl.handle.net/2262/90022
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Toronto
14.
Baglaenko, Yuriy.
Dissecting the Genetics and Function of CD5+ B and invariant NKT cells using Congenic Lupus-Prone Mouse Strains.
Degree: PhD, 2017, University of Toronto
URL: http://hdl.handle.net/1807/77442
► Systemic lupus erythematosus (SLE) is a complex multisystem autoimmune disorder characterized by the production of antibodies to nuclear antigens. Congenic strains derived from lupus-prone mice…
(more)
▼ Systemic lupus erythematosus (SLE) is a complex multisystem autoimmune disorder characterized by the production of antibodies to nuclear antigens. Congenic strains derived from lupus-prone mice have been extremely useful in determining the pathogenesis of this condition. These mice, which harbor selected genetic elements containing susceptibility loci, can be used to identify key pathways and immune networks involved in disease initiation and progression. Alternatively, these same models can be used to identify the role of suppressive regulatory
cells involved in preventing disease. In this thesis, the role and function of CD5+ and invariant Natural Killer T (iNKT) innate lymphocytes were investigated in the suppression of disease in New Zealand Black lupus-prone congenic mice. Through adoptive transfer and knockout experiments, CD5+ B
cells, but not iNKT
cells, were shown to suppress autoimmunity by inhibiting the frequencies of proinflammatory T cell subsets. As these CD5+ B
cells secreted IL-10, which has been shown previously to suppress disease, the role of this cytokine was further investigated through knockout experiments that highlighted its critical role in maintaining CD5+ B, iNKT, and Natural Killer cell homeostasis. Finally, the immunogenetic basis of impaired iNKT cell function in the congenic mouse strains was investigated, revealing a critical role for Ly108 in iNKT cell development and function. Collectively, these findings highlight the role of CD5+ B
cells and iNKT
cells in SLE pathogenesis and demonstrate the power of congenic animals to dissect the genetic basis of disease.
Advisors/Committee Members: Wither, Joan E, Immunology.
Subjects/Keywords: Autoimmunity; B1a; B cells; Congenics; NKT; NZB; 0982
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APA ·
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MLA ·
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Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Baglaenko, Y. (2017). Dissecting the Genetics and Function of CD5+ B and invariant NKT cells using Congenic Lupus-Prone Mouse Strains. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/77442
Chicago Manual of Style (16th Edition):
Baglaenko, Yuriy. “Dissecting the Genetics and Function of CD5+ B and invariant NKT cells using Congenic Lupus-Prone Mouse Strains.” 2017. Doctoral Dissertation, University of Toronto. Accessed April 17, 2021.
http://hdl.handle.net/1807/77442.
MLA Handbook (7th Edition):
Baglaenko, Yuriy. “Dissecting the Genetics and Function of CD5+ B and invariant NKT cells using Congenic Lupus-Prone Mouse Strains.” 2017. Web. 17 Apr 2021.
Vancouver:
Baglaenko Y. Dissecting the Genetics and Function of CD5+ B and invariant NKT cells using Congenic Lupus-Prone Mouse Strains. [Internet] [Doctoral dissertation]. University of Toronto; 2017. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/1807/77442.
Council of Science Editors:
Baglaenko Y. Dissecting the Genetics and Function of CD5+ B and invariant NKT cells using Congenic Lupus-Prone Mouse Strains. [Doctoral Dissertation]. University of Toronto; 2017. Available from: http://hdl.handle.net/1807/77442
University of Melbourne
15.
Fletcher, Marie Therese.
Functional and developmental analyses of NKT cell subsets.
Degree: 2010, University of Melbourne
URL: http://hdl.handle.net/11343/35426
► NKT cells are a population of T cells that have a broad range of regulatory effects on the immune system. Somewhat paradoxically, they can both…
(more)
▼ NKT cells are a population of T cells that have a broad range of regulatory effects on the immune system. Somewhat paradoxically, they can both suppress and potentiate cell-mediated immune responses; for example, while they can suppress some autoimmune diseases, they can also promote potent tumour rejection. There is accumulating evidence to suggest that this functional dichotomy can be explained by the existence of functionally distinct NKT cell subsets, which can differentially regulate the behaviour of other immune cells and drive remarkably different outcomes in disease settings.
Studies in vivo and in vitro have demonstrated remarkable functional diversity between NKT cell subsets of different phenotypes, and deriving from different tissues. This thesis examined functional differences between NKT cell subsets in the context of type 1 diabetes in NOD mice, identified a phenotypically and developmentally distinct IL-17 producing NKT cell subset, and investigated the functional effects of thymic NKT cells on the development and maintenance of conventional T cells and thymic stromal cells. The data presented in this thesis adds to the accumulating evidence that NKT cells are a functionally heterogeneous population, and reiterates the important point that subsets of NKT cells should be studied separately in order to properly understand the biological function of this important regulatory T cell population, and to maximise their clinical potential.
Subjects/Keywords: NKT cells; immune regulation
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APA (6th Edition):
Fletcher, M. T. (2010). Functional and developmental analyses of NKT cell subsets. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/35426
Chicago Manual of Style (16th Edition):
Fletcher, Marie Therese. “Functional and developmental analyses of NKT cell subsets.” 2010. Doctoral Dissertation, University of Melbourne. Accessed April 17, 2021.
http://hdl.handle.net/11343/35426.
MLA Handbook (7th Edition):
Fletcher, Marie Therese. “Functional and developmental analyses of NKT cell subsets.” 2010. Web. 17 Apr 2021.
Vancouver:
Fletcher MT. Functional and developmental analyses of NKT cell subsets. [Internet] [Doctoral dissertation]. University of Melbourne; 2010. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/11343/35426.
Council of Science Editors:
Fletcher MT. Functional and developmental analyses of NKT cell subsets. [Doctoral Dissertation]. University of Melbourne; 2010. Available from: http://hdl.handle.net/11343/35426
Wright State University
16.
Oulad Abdelati, Howaida A.
Type I Interferon Activation of Natural Killer (NK) Cells by
Cytomegalovirus (CMV) and Their Interaction with Dendritic (DC) and
NKT Cells.
Degree: MS, Microbiology and Immunology, 2013, Wright State University
URL: http://rave.ohiolink.edu/etdc/view?acc_num=wright1389625313
► In our current study the roles of natural killer (NK) cells in regulation of the acute phase of murine cytomegalovirus (MCMV) infection were demonstrated. NK…
(more)
▼ In our current study the roles of natural killer (NK)
cells in regulation of the acute phase of murine cytomegalovirus
(MCMV) infection were demonstrated. NK
cells utilize perforin and
gamma interferon to kill MCMV infected
cells. Activation of NK
cells is controlled by the balance between inhibitory and
activation receptors and modulated by cytokines produced from the
infected
cells. Type I interferons are produced mainly by
plasmacytoid dendritic
cells (PDCs). Type I interferons have a
substantial role in enhancing NK
cells cytotoxic activity and NK
cells proliferation and maintain cell survival through STAT
mediated signaling pathway. IL-12 produced by dendritic
cells
activates NK
cells and natural killer T (
NKT)
cells. Natural killer
T
cells activate NK
cells through IFN-Y production at early time
during MCMV infection. These immune
cells and their produced
cytokines are critical to regulate MCMV infection and any
disturbance of this activation will lead to impaired host innate
immunity.
Advisors/Committee Members: Bigley, Nancy (Advisor).
Subjects/Keywords: Microbiology; Immunology; NK cells; MCMV; NKT; PDCs; Type I interferon
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APA (6th Edition):
Oulad Abdelati, H. A. (2013). Type I Interferon Activation of Natural Killer (NK) Cells by
Cytomegalovirus (CMV) and Their Interaction with Dendritic (DC) and
NKT Cells. (Masters Thesis). Wright State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=wright1389625313
Chicago Manual of Style (16th Edition):
Oulad Abdelati, Howaida A. “Type I Interferon Activation of Natural Killer (NK) Cells by
Cytomegalovirus (CMV) and Their Interaction with Dendritic (DC) and
NKT Cells.” 2013. Masters Thesis, Wright State University. Accessed April 17, 2021.
http://rave.ohiolink.edu/etdc/view?acc_num=wright1389625313.
MLA Handbook (7th Edition):
Oulad Abdelati, Howaida A. “Type I Interferon Activation of Natural Killer (NK) Cells by
Cytomegalovirus (CMV) and Their Interaction with Dendritic (DC) and
NKT Cells.” 2013. Web. 17 Apr 2021.
Vancouver:
Oulad Abdelati HA. Type I Interferon Activation of Natural Killer (NK) Cells by
Cytomegalovirus (CMV) and Their Interaction with Dendritic (DC) and
NKT Cells. [Internet] [Masters thesis]. Wright State University; 2013. [cited 2021 Apr 17].
Available from: http://rave.ohiolink.edu/etdc/view?acc_num=wright1389625313.
Council of Science Editors:
Oulad Abdelati HA. Type I Interferon Activation of Natural Killer (NK) Cells by
Cytomegalovirus (CMV) and Their Interaction with Dendritic (DC) and
NKT Cells. [Masters Thesis]. Wright State University; 2013. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=wright1389625313
University of Manchester
17.
Gieschen-Krische, Mary.
The role of NKT cells following solid organ transplantation.
Degree: PhD, 2014, University of Manchester
URL: https://www.research.manchester.ac.uk/portal/en/theses/the-role-of-nkt-cells-following-solid-organ-transplantation(321a0a4b-336e-44dd-a608-58f7ea58e27e).html
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764287
► Introduction: NKT cells are categorised as borderline between NK and T cells, sharing phenotypic and functional characteristics of both cells, demonstrating their capacity to contritube…
(more)
▼ Introduction: NKT cells are categorised as borderline between NK and T cells, sharing phenotypic and functional characteristics of both cells, demonstrating their capacity to contritube to both pro- or anti-inflammatory processes. However, the role of these cells among lung transplant recipients remains largely unknown. The aim of this study was to determine the role of NKT cells following lung transplantation. Methods: NKT cells were quantified and characterised according to markers of: activation (CD107a, CD161, NKG2D) and immunomodulation (CD200 and CD200R) in peripheral blood and BALs. NKT cell numbers and phenotypes were correlated to clinical variables: immunosuppression, acute rejection, acute infections (viral, bacterial and fungal), bronchiolitis obliterans syndrome (BOS grade), lung function, and demographic variables. Interactions between NKT cells and the transplanted lung were linked by determining the relative expression of immunomodulatory ligand CD200 in lung biopsies. In vitro models were employed to determine the role of NKT cells to acute lung injury, either alone or in combination with cells of the mononuclear phagocyte system (MPS). Results: Higher numbers of immunomodulatory NKT cells (CD200+ and CD200R+) were found as lung function decreased. Data from peripheral blood indicates that recipients whose donors or themselves had been exposed to CMV infection demonstrated increased numbers of NKT cells. Patients with active EBV infections demonstrated higher NKT cell numbers expressing CD200 and CD200R. Data from BALs, indicates that patients with active fungal infections present higher immunomodulatory (CD200R) NKT cells and lower cytotoxicity marker (CD107a). In peripheral blood, lung recipients demonstrated higher NKT cell numbers compared to healthy volunteers. However, the lower relative mean expression of functional markers in the lung transplant group suggests that cells are less active. In vitro cultures with immunosuppressants demonstrated that cell cycle inhibitors (MMF and AZA) and corticosteroids (Prednisolone) are likely to inhibit NKT cell proliferation, while calcineurin inhibitors (Cyclosporine A and Tacrolimus) decrease the relative mean expression of activation markers. Clinical observations indicate that higher doses of Azathioprine may correlate with increased NKT cell numbers and the relative expression of CD200 and CD200R. However, under these conditions the relative expression of activation marker NKG2D decreases. In vitro data from the acute injury model indicates that NKT cells are capable to migrate into the injured lung and become activated following transmigration which is facilitated by the presence of monocytes. We also observed the interaction of NKT cells with endothelial cells, monocytes and macrophages. Also, the relative mean expression of CD200 and CD200R increased at the capillary layer, regardless of injury while upregulation of activation markers (CD107a, CD161 and NKG2D) was found at the capillary layer, following injury. In contrast, the alveolar layer…
Subjects/Keywords: 617.5; acute lung injury; immunosuppression; NKT cells; lung; transplantation
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APA (6th Edition):
Gieschen-Krische, M. (2014). The role of NKT cells following solid organ transplantation. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/the-role-of-nkt-cells-following-solid-organ-transplantation(321a0a4b-336e-44dd-a608-58f7ea58e27e).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764287
Chicago Manual of Style (16th Edition):
Gieschen-Krische, Mary. “The role of NKT cells following solid organ transplantation.” 2014. Doctoral Dissertation, University of Manchester. Accessed April 17, 2021.
https://www.research.manchester.ac.uk/portal/en/theses/the-role-of-nkt-cells-following-solid-organ-transplantation(321a0a4b-336e-44dd-a608-58f7ea58e27e).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764287.
MLA Handbook (7th Edition):
Gieschen-Krische, Mary. “The role of NKT cells following solid organ transplantation.” 2014. Web. 17 Apr 2021.
Vancouver:
Gieschen-Krische M. The role of NKT cells following solid organ transplantation. [Internet] [Doctoral dissertation]. University of Manchester; 2014. [cited 2021 Apr 17].
Available from: https://www.research.manchester.ac.uk/portal/en/theses/the-role-of-nkt-cells-following-solid-organ-transplantation(321a0a4b-336e-44dd-a608-58f7ea58e27e).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764287.
Council of Science Editors:
Gieschen-Krische M. The role of NKT cells following solid organ transplantation. [Doctoral Dissertation]. University of Manchester; 2014. Available from: https://www.research.manchester.ac.uk/portal/en/theses/the-role-of-nkt-cells-following-solid-organ-transplantation(321a0a4b-336e-44dd-a608-58f7ea58e27e).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764287
University of Oxford
18.
Crawford, Greg Hugh.
The role of DOCK8 in the maintenance of CD8+ T cell memory and invariant NKT cells.
Degree: PhD, 2012, University of Oxford
URL: http://ora.ox.ac.uk/objects/uuid:771febbe-ec6e-4e7b-9b6e-35b95d040b1a
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.581108
► The use of genome wide ENU mutagenesis screening has uncovered vast numbers of novel genes involved in the control of the immune system. This thesis…
(more)
▼ The use of genome wide ENU mutagenesis screening has uncovered vast numbers of novel genes involved in the control of the immune system. This thesis describes the characterization of a novel mutant, Captain Morgan (CPM), originally identified in an immunization screen designed to evaluate both the initial antibody response to antigen and the ability to sustain antibody production. Mapping of this mutant lead to the identification of a single base pair mutation in a novel guanine nucleotide exchange factor, dedicator of cytokinesis 8 (DOCK8). The mutation was found to result in altered gene splicing of the DOCK8 protein leading to the truncation of the protein and loss of catalytic function. The importance of understanding the role of DOCK8 in host immunity has been recently underlined by the discovery that cohorts of patients suffering from autosomal recessive forms of hyper-IgE syndrome have loss-of-function or deletions in this novel guanine nucleotide exchange factor. Disease in these patients is characterised by recurrent viral and bacterial infections mainly of the skin and lungs, with reduced levels of peripheral CD4+ and CD8+ T cells in the blood of patients. Patients also have high levels of IgE and eosinophilia in the blood and are highly atopic with increased prevalence of allergic diseases including asthma. Loss of DOCK8 function results in a number of phenotypes in CPM mice, which may help understand the immunodeficiency syndrome experienced by DOCK8 deficient patients. CPM mice, like DOCK8 deficient patients, are lymphopenic with losses of both CD4+ and CD8+ T cells in the blood and secondary lymphoid organs. Challenge of CPM mice with modified vaccina virus (MVA) and influenza strain X31 demonstrated normal primary anti-viral responses. However, similar to the loss of germinal centre B cells previously described in these mice, memory T cell responses were diminished, which may explain the susceptibility of DOCK8 deficient patients to recurrent infections. In addition to the loss of peripheral T cells, rare populations of lymphocytes such as invariant natural killer T cells (iNKT) were also reduced in the liver and thymus. Due to their roles in bacterial and viral responses and cancer immunosurveillance it is expected that loss of these cells will contribute to disease severity. Together these findings illustrate the importance of the ENU mutagenesis model for generating new mutants, which can enhance our understanding of mammalian genes and create disease models of human disease. Further characterization of DOCK8 deficiency and the molecular mechanisms of DOCK8 function will have important implications for disease diagnosis and ongoing treatment for patients.
Subjects/Keywords: 616.079; Biology; Genetics (life sciences); Transgenics; Immunology; Infectious diseases; NKT cells; memory CD8 T cells
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APA (6th Edition):
Crawford, G. H. (2012). The role of DOCK8 in the maintenance of CD8+ T cell memory and invariant NKT cells. (Doctoral Dissertation). University of Oxford. Retrieved from http://ora.ox.ac.uk/objects/uuid:771febbe-ec6e-4e7b-9b6e-35b95d040b1a ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.581108
Chicago Manual of Style (16th Edition):
Crawford, Greg Hugh. “The role of DOCK8 in the maintenance of CD8+ T cell memory and invariant NKT cells.” 2012. Doctoral Dissertation, University of Oxford. Accessed April 17, 2021.
http://ora.ox.ac.uk/objects/uuid:771febbe-ec6e-4e7b-9b6e-35b95d040b1a ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.581108.
MLA Handbook (7th Edition):
Crawford, Greg Hugh. “The role of DOCK8 in the maintenance of CD8+ T cell memory and invariant NKT cells.” 2012. Web. 17 Apr 2021.
Vancouver:
Crawford GH. The role of DOCK8 in the maintenance of CD8+ T cell memory and invariant NKT cells. [Internet] [Doctoral dissertation]. University of Oxford; 2012. [cited 2021 Apr 17].
Available from: http://ora.ox.ac.uk/objects/uuid:771febbe-ec6e-4e7b-9b6e-35b95d040b1a ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.581108.
Council of Science Editors:
Crawford GH. The role of DOCK8 in the maintenance of CD8+ T cell memory and invariant NKT cells. [Doctoral Dissertation]. University of Oxford; 2012. Available from: http://ora.ox.ac.uk/objects/uuid:771febbe-ec6e-4e7b-9b6e-35b95d040b1a ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.581108
19.
Weinkove, Robert.
Invariant Natural Killer T Cells in Chronic Lymphocytic Leukaemia
.
Degree: 2012, University of Otago
URL: http://hdl.handle.net/10523/2624
► Invariant natural killer T (iNKT) cells recognise glycolipid antigens, such as the synthetic ligand alpha galactosylceramide (a-GalCer), in the context of CD1d. Upon recognition of…
(more)
▼ Invariant natural killer T (iNKT)
cells recognise glycolipid antigens, such as the synthetic ligand alpha galactosylceramide (a-GalCer), in the context of CD1d. Upon recognition of a-GalCer on CD1d, iNKT
cells become activated and rapidly produce cytokines. Recruitment of iNKT
cells with a-GalCer results in potent antitumour activity in some pre-clinical cancer models. Effector mechanisms include direct cytotoxicity of iNKT
cells against CD1d-expressing tumours in the presence of a-GalCer, transactivation of natural killer
cells by iNKT cell-derived interferon gamma, and iNKT cell-induced maturation and activation of dendritic
cells (DCs), leading to enhanced T cell responses to DC-presented peptides.
Chronic lymphocytic leukaemia (CLL) is a clonal malignancy of B lymphocytes. Chemotherapy induces remission in most patients, but most eventually relapse. Allogeneic stem cell transplantation can be curative, but is not available to most patients due to advanced age or co-morbidities. Thus, CLL is an attractive candidate for cancer immunotherapy. This thesis aims to assess the iNKT cell/CD1d axis of patients, and to explore the possibility of exploiting iNKT
cells for the immunotherapy of CLL.
Peripheral blood mononuclear
cells (PBMCs) were isolated from patients with CLL, and from healthy age-matched controls, and analysed by flow cytometry. Absolute number and phenotype of circulating iNKT
cells was similar in patients and controls, although patients exhibited a relative reduction in iNKT
cells due to expansion of other T cell populations. iNKT cell frequency did not correlate with disease stage or with subsequent progression-free survival in patients with untreated CLL. Expression of CD1d on dendritic
cells and monocytes from patients with CLL was similar to controls.
The cytokine profile of patient iNKT
cells was similar to that of controls. In vitro proliferation of invariant natural killer T (iNKT)
cells from patients with CLL was preserved, and iNKT cell lines generated from patients exhibited cytokine and cytotoxicity profiles similar to those from healthy controls, producing both Th1- and Th2-type cytokines, and lysing a target cell in a CD1d- and a-GalCer-dependent manner. Lysis of autologous CLL
cells by iNKT cell lines was inefficient.
In vitro vaccine recall responses were enhanced by a-GalCer in PBMCs containing high frequencies of iNKT
cells. The treatment of leukaemic
cells with a-GalCer enhanced their ability to stimulate proliferation of allogeneic PBMCs from healthy donors in vitro, largely due to iNKT cell proliferation. Leukaemic
cells treated with a-GalCer induced proliferation of autologous iNKT
cells, and a-GalCer treatment also led to enhanced proliferation of ‘conventional’ T
cells.
These results indicate that the iNKT cell/CD1d axis is largely intact in patients with CLL and suggest that if low iNKT cell frequencies can be overcome, the adjuvant activity of iNKT
cells might be exploited in cellular immunotherapy of CLL, for example by employing a-GalCer-pulsed leukaemic
cells as a whole…
Advisors/Committee Members: Ronchese, Franca (advisor).
Subjects/Keywords: alpha galactosylceramide;
natural killer T cells;
NKT cells;
chronic lymphocytic leukaemia;
immunotherapy;
invariant natural killer T cells;
human;
CD1d;
glycolipids
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APA ·
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MLA ·
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CSE |
Export
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Manager
APA (6th Edition):
Weinkove, R. (2012). Invariant Natural Killer T Cells in Chronic Lymphocytic Leukaemia
. (Doctoral Dissertation). University of Otago. Retrieved from http://hdl.handle.net/10523/2624
Chicago Manual of Style (16th Edition):
Weinkove, Robert. “Invariant Natural Killer T Cells in Chronic Lymphocytic Leukaemia
.” 2012. Doctoral Dissertation, University of Otago. Accessed April 17, 2021.
http://hdl.handle.net/10523/2624.
MLA Handbook (7th Edition):
Weinkove, Robert. “Invariant Natural Killer T Cells in Chronic Lymphocytic Leukaemia
.” 2012. Web. 17 Apr 2021.
Vancouver:
Weinkove R. Invariant Natural Killer T Cells in Chronic Lymphocytic Leukaemia
. [Internet] [Doctoral dissertation]. University of Otago; 2012. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/10523/2624.
Council of Science Editors:
Weinkove R. Invariant Natural Killer T Cells in Chronic Lymphocytic Leukaemia
. [Doctoral Dissertation]. University of Otago; 2012. Available from: http://hdl.handle.net/10523/2624
Universiteit Utrecht
20.
Sillé, F.C.
Functional requirements for CD1 in development and function of invariant Natural Killer T (iNKT) cells.
Degree: 2010, Universiteit Utrecht
URL: http://dspace.library.uu.nl:8080/handle/1874/42712
► Activation of the adaptive immune response primarily depends on the presentation of peptide antigens via Class I and II major histocompatibility (MHC) complexes. However, some…
(more)
▼ Activation of the adaptive immune response primarily depends on the presentation of peptide antigens via Class I and II major histocompatibility (MHC) complexes. However, some pathogens and tumor
cells have evolved evasive mechanisms to escape these ‘conventional routes’ of antigen presentation. The research described in this thesis focuses on the ‘alternative route’ of lipid antigen presentation on CD1d molecules for the development of invariant Natural Killer T (iNKT)
cells and their activation during pathogenic and autoimmune diseases. Activated iNKT
cells represent highly potent immunoregulatory
cells, stimulating both innate and adaptive immune responses, which makes them attractive targets for immunotherapy. It is therefore, important to understand the mechanisms behind the development and activation of iNKT
cells. Thymic selection and peripheral maturation of iNKT
cells in mice requires CD1d presentation of antigen acquired in endosomal compartments. CD1d molecules reach these compartments through their intrinsic tyrosine motif and by association with the Class II MHC chaperone, invariant chain (Ii). Using a new mouse model in which all CD1d is replaced by CD1d-enhanced yellow fluorescent fusion protein (EYFP), we clarified that the CD1d-encoded tyrosine motif influences the thymic selection of iNKT
cells, but is dispensable for their peripheral maturation. In combination with mouse models deficient for Ii or the Ii-processing enzyme cathepsin S (CatS), we showed that both the CD1d-encoded and Ii-encoded endosomal sorting motifs are necessary for peripheral activation of iNKT
cells and that thymic selection of iNKT
cells not only occurs on CD4+CD8+ thymocytes but also on Ii and CatS-expressing
cells. Patients with deletions or mutations in the CD1d tyrosine motif, invariant chain, or accessory molecules that interact with the cytosolic tail of CD1d, could therefore display severe iNKT cell deficiencies and susceptibility to certain pathogen infections. Invariant
NKT cells play a role in the early immune response against Mycobacterium tuberculosis (Mtb) by suppressing intracellular bacterial growth when activated by antigenic CD1d/lipid complexes on Mtb-infected
cells. Mtb, which causes one of the most prevalent deadly diseases, tuberculosis, avoids degradation by preventing fusion of phagosomes with lysosomal compartments. Using Ii-deficient mice, we demonstrated that Mtb replication occurs in lysosomes and requires Ii-mediated phagolysosomal fusion. However, we also showed that lysosomal presence of Mtb is equally pivotal for induction of CD1d-dependent iNKT cell responses in the host. Lysosomes could therefore be a potential target in the development of therapeutic strategies against Mtb infections. Invariant
NKT cells also regulate immune tolerance as during autoimmunity and inflammation. Using transferrin-ovalbumin (Tf-mOVA) mice as an autoimmune hepatitis model, we demonstrate how rapid cytokine production by activated CD1d-restricted iNKT
cells stimulates intrahepatic CD8+ T cell effector responses to…
Advisors/Committee Members: Prakken, A.B.J., Boes, M.L..
Subjects/Keywords: Geneeskunde; CD1; lipid antigen presentation; intracellular trafficking; invariant NKT cells; Mycobacterium tuberculosis; autoimmune hepatitis
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APA ·
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Export
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Manager
APA (6th Edition):
Sillé, F. C. (2010). Functional requirements for CD1 in development and function of invariant Natural Killer T (iNKT) cells. (Doctoral Dissertation). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/42712
Chicago Manual of Style (16th Edition):
Sillé, F C. “Functional requirements for CD1 in development and function of invariant Natural Killer T (iNKT) cells.” 2010. Doctoral Dissertation, Universiteit Utrecht. Accessed April 17, 2021.
http://dspace.library.uu.nl:8080/handle/1874/42712.
MLA Handbook (7th Edition):
Sillé, F C. “Functional requirements for CD1 in development and function of invariant Natural Killer T (iNKT) cells.” 2010. Web. 17 Apr 2021.
Vancouver:
Sillé FC. Functional requirements for CD1 in development and function of invariant Natural Killer T (iNKT) cells. [Internet] [Doctoral dissertation]. Universiteit Utrecht; 2010. [cited 2021 Apr 17].
Available from: http://dspace.library.uu.nl:8080/handle/1874/42712.
Council of Science Editors:
Sillé FC. Functional requirements for CD1 in development and function of invariant Natural Killer T (iNKT) cells. [Doctoral Dissertation]. Universiteit Utrecht; 2010. Available from: http://dspace.library.uu.nl:8080/handle/1874/42712
Vanderbilt University
21.
Gordy, Laura Elizabeth.
Repertoire selection and effector differentiation during NKT cell development.
Degree: PhD, Microbiology and Immunology, 2012, Vanderbilt University
URL: http://hdl.handle.net/1803/11710
► Natural killer T (NKT) cells are innate-like lymphocytes that develop and mature in the thymus. From there, they home to the peripheral lymphoid tissues where,…
(more)
▼ Natural killer T (
NKT)
cells are innate-like lymphocytes that develop and mature in the thymus. From there, they home to the peripheral lymphoid tissues where, in some cases, they can finalise the maturation program.
NKT cells function by close cell-cell interactions with antigen presenting
cells and upon activation release copious amounts of proinflammatory and immunoregulatory cytokines and chemokines.
NKT cells acquire their functions during development. I address two questions in this dissertation: (a) the role of negative selection in sculpting a functional
NKT cell repertoire; and (b) the role of interleukin (IL)-15 in
NKT cell effector differentiation and homeostasis. My studies generated mouse models for overt or impaired negative selection and revealed direct evidence for negative selection in sculpting the semi-invariant T cell receptor repertoire of
NKT cells. Nonetheless, the effect of negative selection, as probed using currently known
NKT cell agonists, was subtle in that it had modest effects on
NKT cell function. The most significant advance I made is related to an understanding of cytokine signals that induce
NKT cell effector differentiation and how these signals are integrated to affect this outcome. I discovered that IL-15 plays a pivotal role in signalling
NKT cell survival through the induction of Bcl-2 family member Bcl-xL. Rescue of
NKT cell development by enforced Bcl-xL expression in IL-15 deficient mouse thymocytes exposed an additional role of IL-15 in inducing terminal maturation and effector differentiation of
NKT cells. Gene expression analysis indicated that IL-15 regulated Tbx21 (T-bet) expression and that of T-bet-regulated genes, including those that mediate effector functions of
NKT cells. Because T-bet was previously shown to regulate terminal maturation and effector differentiation of
NKT cells, I conclude that IL-15 mediates its functions within
NKT cells at least in part through regulated expression of T-bet. Thus, my findings have revealed important new insights into signals that regulate the development of functional
NKT cells.
Advisors/Committee Members: Sebastian Joyce (committee member), Ann Richmond (committee member), Eric Sebzda (committee member), Mark Boothby (committee member), Luc Van Kaer (Committee Chair).
Subjects/Keywords: T-bet; IL-15; Bcl-xL; development; survival; NKT cells; Nur77; negative selection
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APA ·
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MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Gordy, L. E. (2012). Repertoire selection and effector differentiation during NKT cell development. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/11710
Chicago Manual of Style (16th Edition):
Gordy, Laura Elizabeth. “Repertoire selection and effector differentiation during NKT cell development.” 2012. Doctoral Dissertation, Vanderbilt University. Accessed April 17, 2021.
http://hdl.handle.net/1803/11710.
MLA Handbook (7th Edition):
Gordy, Laura Elizabeth. “Repertoire selection and effector differentiation during NKT cell development.” 2012. Web. 17 Apr 2021.
Vancouver:
Gordy LE. Repertoire selection and effector differentiation during NKT cell development. [Internet] [Doctoral dissertation]. Vanderbilt University; 2012. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/1803/11710.
Council of Science Editors:
Gordy LE. Repertoire selection and effector differentiation during NKT cell development. [Doctoral Dissertation]. Vanderbilt University; 2012. Available from: http://hdl.handle.net/1803/11710
University of Toronto
22.
Gunst, Christopher James.
Defining Notch Functions in the Development of Innate T Cells.
Degree: 2016, University of Toronto
URL: http://hdl.handle.net/1807/79735
► Innate T cells, which include PLZF+ T cells and innate memory CD8 SPs, represent a unique lineage of T cells that are pre-activated and rapidly…
(more)
▼ Innate T cells, which include PLZF+ T cells and innate memory CD8 SPs, represent a unique lineage of T cells that are pre-activated and rapidly respond to antigen. Although the role of Notch in early T cell development is well-established, its function in late T cell development, when innate T cells arise, is unclear. Here, we report that CD4-Cre-mediated intracellular Notch1 expression (ICN1) increased the non-cell autonomous development of innate memory CD8 SPs. ICN1-expression also increased the frequency of NKT2 cells and number of V6 γδ T cells in the thymus, which are specific PLZF-expressing innate T cell subsets suggested to drive innate memory CD8 SP development through IL-4 secretion. Collectively, my data demonstrates that Notch signaling is an important regulator of innate T cell development and emphasizes its role in late T cell development.
M.Sc.
Advisors/Committee Members: Guidos, Cynthia J, Immunology.
Subjects/Keywords: IL-4; Innate memory; NKT Cells; Notch; PLZF; V6 γδ T cell; 0982
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APA (6th Edition):
Gunst, C. J. (2016). Defining Notch Functions in the Development of Innate T Cells. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/79735
Chicago Manual of Style (16th Edition):
Gunst, Christopher James. “Defining Notch Functions in the Development of Innate T Cells.” 2016. Masters Thesis, University of Toronto. Accessed April 17, 2021.
http://hdl.handle.net/1807/79735.
MLA Handbook (7th Edition):
Gunst, Christopher James. “Defining Notch Functions in the Development of Innate T Cells.” 2016. Web. 17 Apr 2021.
Vancouver:
Gunst CJ. Defining Notch Functions in the Development of Innate T Cells. [Internet] [Masters thesis]. University of Toronto; 2016. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/1807/79735.
Council of Science Editors:
Gunst CJ. Defining Notch Functions in the Development of Innate T Cells. [Masters Thesis]. University of Toronto; 2016. Available from: http://hdl.handle.net/1807/79735
University of Lund
23.
Teige, Anna.
CD1d restricted NKT cells in regulation of pathogenic
autoimmunity.
Degree: 2014, University of Lund
URL: https://lup.lub.lu.se/record/4294855
;
https://portal.research.lu.se/ws/files/3032603/4300856.pdf
► Human autoimmune diseases such as reumatoid arthritis (RA) and multiple sclerosis (MS) are believed to develop when self-tolerance mechanisms are failing, with a chronic destructive…
(more)
▼ Human autoimmune diseases such as reumatoid
arthritis (RA) and multiple sclerosis (MS) are believed to develop
when self-tolerance mechanisms are failing, with a chronic
destructive inflammation as result. To experimentally study
autoimmunity, we have used murine models that mimic their human
counterparts; experimental autoimmune encephalomyelitis (EAE) – a
model for MS, and collagen induced arthritis (CIA) and antigen
induced arthritis (AIA) – models for RA. A sub-population of T
cells, termed natural killer T cells (NKT), have been suggested as
having immunoregulatory features in pathogenic autoimmunity. How
NKT cells are activated to perform this regulation and by which
functional pathways they act is not completely understood. A number
of natural antigens activating NKT cells via the antigen presenting
molecule CD1d have so far been identified as glycolipids
originating from either bacteria or self. This thesis investigates
the role of NKT cells in autoimmune tissue-specific inflammation.
We found that NKT cells can down-regulate both the central nervous
system-specific autoimmunity in EAE, and the joint-specific
inflammation in experimentally induced arthritis. We also show data
indicating that this regulation requires activation in the
periphery, and we have identified a natural self-peptide capable of
exerting this activation; A CD1d restricted peptide derived from
autologous collagen type II. By vaccinating mice with this peptide
we were able to ameliorate the inflammation and reduce the disease
phenotype in both CIA and EAE. We also found the peptide-specific
NKT cells capable of suppressing activated T cells in vitro. Taken
together, this thesis show that CD1d restricted NKT cells can be
activated to down-regulate pathogenic autoimmunity, and should be
investigated as targets for future autoimmune
therapies.
Subjects/Keywords: Other Clinical Medicine; Autoimmunity; NKT cells; CD1d antigen presentation; Multiple sclerosis; Rheumatoid arthritis
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Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Teige, A. (2014). CD1d restricted NKT cells in regulation of pathogenic
autoimmunity. (Doctoral Dissertation). University of Lund. Retrieved from https://lup.lub.lu.se/record/4294855 ; https://portal.research.lu.se/ws/files/3032603/4300856.pdf
Chicago Manual of Style (16th Edition):
Teige, Anna. “CD1d restricted NKT cells in regulation of pathogenic
autoimmunity.” 2014. Doctoral Dissertation, University of Lund. Accessed April 17, 2021.
https://lup.lub.lu.se/record/4294855 ; https://portal.research.lu.se/ws/files/3032603/4300856.pdf.
MLA Handbook (7th Edition):
Teige, Anna. “CD1d restricted NKT cells in regulation of pathogenic
autoimmunity.” 2014. Web. 17 Apr 2021.
Vancouver:
Teige A. CD1d restricted NKT cells in regulation of pathogenic
autoimmunity. [Internet] [Doctoral dissertation]. University of Lund; 2014. [cited 2021 Apr 17].
Available from: https://lup.lub.lu.se/record/4294855 ; https://portal.research.lu.se/ws/files/3032603/4300856.pdf.
Council of Science Editors:
Teige A. CD1d restricted NKT cells in regulation of pathogenic
autoimmunity. [Doctoral Dissertation]. University of Lund; 2014. Available from: https://lup.lub.lu.se/record/4294855 ; https://portal.research.lu.se/ws/files/3032603/4300856.pdf
University of Lund
24.
Nilsson, Julia.
Cellular and molecular mechanisms in immune mediated
hepatic fibrosis. A study of the inflammatory syndrome and fibrosis
development of the NIF mouse liver.
Degree: 2020, University of Lund
URL: https://lup.lub.lu.se/record/8424880b-513b-4edd-9f0e-0cbce745413f
;
https://portal.research.lu.se/ws/files/78828800/Julia_Nilsson_dissertation_for_web.pdf
► Fibrosis is the result of dysregulated inflammation and tissue repair, and is characterized by the excessive accumulation of extra cellular matrix (ECM) proteins. It causes…
(more)
▼ Fibrosis is the result of dysregulated inflammation
and tissue repair, and is characterized by the excessive
accumulation of extra cellular matrix (ECM) proteins. It causes
detrimental effects to the afflicted tissue and can subsequently
lead to organ failure. Sterile liver inflammation and hepatic
fibrosis are associated with many liver disorders of different
etiologies. Both type 1 and type 2 inflammatory responses have been
reported to contribute to the pathology, however, the mechanisms
controlling the balance between them are largely unknown. A major
limitation in the attempts to understand the underlying mechanisms
leading to fibrosis development, and to establish efficient
anti-fibrotic treatment protocols has been the restricted set of
suitable animal models available. In paper I, we characterize the
NIF mouse, a recently established animal model that spontaneously
develops chronic inflammation and fibrosis in the liver. The
inflammatory syndrome is mediated by a transgenic population of
Natural Killer T (NKT) cells induced on an immunodeficient NOD
genetic background and is characterized by the combined production
of both TH1 and TH2 cytokines. We show that the disease is
transferrable to immunodeficient recipients, while polyclonal T
cells from unaffected syngeneic donors can reverse the disease
phenotype.In paper II, we demonstrate that the transgenic NKT cells
of the NIF mouse mediate the initiation of a chronic type 1
inflammatory response in the liver, involving the activation of the
NLRP3 inflammasome. A subsequent shift into a type 2 inflammatory
response, driven by the production of IL-33, activation of hepatic
stellate cells (HSC) and production of
anti-inflammatory/pro-fibrotic cytokines by the same transgenic NKT
cell population, promotes the development of hepatic fibrosis. This
data illustrates how plasticity in NKT cells can drive an initial
type 1 inflammatory response, as well as promote the transition
into a type 2 inflammatory response.Paper III illustrates how the
NIF mouse model can be used for efficacy testing of drug candidates
against liver fibrosis. It is imperative to develop new and
improved techniques in order to be able to further investigate the
pathophysiological tissue changes caused by fibrosis, as well as
allowing for the possibility to monitor the effects of disease
intervention protocols. In line with this, part of this
dissertation work has been focused on the development of novel
imaging technology for this purpose. In paper IV, we demonstrate
how the anterior chamber of the eye (ACE) imaging technique can be
utilized for the longitudinal in vivo study of structural changes
in transplanted tissue. The disease phenotype of the NIF mouse
resembles human fibrotic conditions in several pertinent features,
which offers a unique opportunity to gain further insight into the
underlying mechanisms mediating transformation of chronic
inflammation into development of pathological
fibrosis.
Subjects/Keywords: Immunology in the medical area; Fibrosis; liver; mouse model; NKT cells; type 2 inflammation; inflammasome
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CSE |
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Manager
APA (6th Edition):
Nilsson, J. (2020). Cellular and molecular mechanisms in immune mediated
hepatic fibrosis. A study of the inflammatory syndrome and fibrosis
development of the NIF mouse liver. (Doctoral Dissertation). University of Lund. Retrieved from https://lup.lub.lu.se/record/8424880b-513b-4edd-9f0e-0cbce745413f ; https://portal.research.lu.se/ws/files/78828800/Julia_Nilsson_dissertation_for_web.pdf
Chicago Manual of Style (16th Edition):
Nilsson, Julia. “Cellular and molecular mechanisms in immune mediated
hepatic fibrosis. A study of the inflammatory syndrome and fibrosis
development of the NIF mouse liver.” 2020. Doctoral Dissertation, University of Lund. Accessed April 17, 2021.
https://lup.lub.lu.se/record/8424880b-513b-4edd-9f0e-0cbce745413f ; https://portal.research.lu.se/ws/files/78828800/Julia_Nilsson_dissertation_for_web.pdf.
MLA Handbook (7th Edition):
Nilsson, Julia. “Cellular and molecular mechanisms in immune mediated
hepatic fibrosis. A study of the inflammatory syndrome and fibrosis
development of the NIF mouse liver.” 2020. Web. 17 Apr 2021.
Vancouver:
Nilsson J. Cellular and molecular mechanisms in immune mediated
hepatic fibrosis. A study of the inflammatory syndrome and fibrosis
development of the NIF mouse liver. [Internet] [Doctoral dissertation]. University of Lund; 2020. [cited 2021 Apr 17].
Available from: https://lup.lub.lu.se/record/8424880b-513b-4edd-9f0e-0cbce745413f ; https://portal.research.lu.se/ws/files/78828800/Julia_Nilsson_dissertation_for_web.pdf.
Council of Science Editors:
Nilsson J. Cellular and molecular mechanisms in immune mediated
hepatic fibrosis. A study of the inflammatory syndrome and fibrosis
development of the NIF mouse liver. [Doctoral Dissertation]. University of Lund; 2020. Available from: https://lup.lub.lu.se/record/8424880b-513b-4edd-9f0e-0cbce745413f ; https://portal.research.lu.se/ws/files/78828800/Julia_Nilsson_dissertation_for_web.pdf
University of Melbourne
25.
CAO, BENJAMIN.
Synthesis of immunogenic mycobacterial cell wall glycolipids.
Degree: 2011, University of Melbourne
URL: http://hdl.handle.net/11343/36645
► Mycobacterium tuberculosis, the causitive agent of tuberculosis, possesses a complex cell wall containing mannose-rich glycophospholipids termed phosphatidylinositol mannosides (PIMs), lipomannan (LM), and lipoarabinomannan (LAM). These…
(more)
▼ Mycobacterium tuberculosis, the causitive agent of tuberculosis, possesses a complex cell wall containing mannose-rich glycophospholipids termed phosphatidylinositol mannosides (PIMs), lipomannan (LM), and lipoarabinomannan (LAM). These glycophospholipids are believed to play important roles in cell wall function and hostpathogen interactions. Synthetic PIM/LM/LAM substructures are useful biochemical tools to delineate and dissect the fine details of mannose glycophospholipid biosynthesis and their interactions with host cells. The first part of this thesis describes the efficient synthesis of a series of azidooctyl di- and trimannosides possessing the following glycan structures: alpha-Man-1,6-alpha-Man, alpha-Man-1,6-alpha-Man-1,6-alpha-Man, alpha-Man-1,2-alpha-Man-1,6-alpha-Man and 2,6-di-(alpha-Man)-alpha-Man. Highlights of the synthesis include the use of nonbenzyl protecting groups compatible with the azido group and preparation of the branched trisaccharide structure 2,6-di-(alpha-Man)-alpha-Man through a double glycosylation of a 3,4-butanediacetal-protected mannoside. The hydrophobic azidooctyl aglycon of these compounds confers useful lipophilicity allowing simple extraction of enzymatic products from reaction mixtures. The azidooctyl groups of these synthetic mannans were elaborated to fluorescent neoglycoconjugates and haptens for the study of mycobacterial glycolipid biosynthesis and antigenicity.
The second part of this thesis describes the use of synthetic mycobacterial glycolipid antigens in defining a new population of natural killer T (NKT) cells. NKT cells are a small subpopulation of T lymphocytes that recognize glycolipid antigens when presented by the antigen presenting protein CD1d. The most widely studied subset of NKT cells are termed type I NKT cells and are characterized by the expression of an invariant T cell receptor Valpha14-alpha-chain in mice. When activated, NKT cells produce significant amounts of pro-inflammatory TH1 cytokines and immunosuppressive TH2 cytokines. TH1 cytokines responses are involved in immune defence against microbial, viral and parasitic infections and can be used to treat tumours and cancers. In contrast, TH2 responses are involved in immunoregulation and are implicated in autoimmune diseases such as type I diabetes and rheumatoid arthritis. Identifying new ligands with selective activation properties remains a task of growing importance. Described herein is the synthesis of a mycobacterial glycolipid, Gl-A and two other structural variants, which were used to precisely define the structure of the natural material through collision induced MS. Highlights of the synthesis include a new enantioselective route to (R)-tuberculostearic acid using a chiral auxiliary, and efficient esterification steps using the recently reported peptide coupling reagent COMU. The three Gl-A variants were used to define a new subpopulation of functionally distinct Valpha10 NKT cells, which possesses a unique antigen recognition profile…
Subjects/Keywords: phosphatidylinositol mannosides; lipomannan; lipoarabinomannan; glycosylation; tuberculostearic acid; Gl-A; CD1d; NKT cells
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APA ·
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Manager
APA (6th Edition):
CAO, B. (2011). Synthesis of immunogenic mycobacterial cell wall glycolipids. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/36645
Chicago Manual of Style (16th Edition):
CAO, BENJAMIN. “Synthesis of immunogenic mycobacterial cell wall glycolipids.” 2011. Doctoral Dissertation, University of Melbourne. Accessed April 17, 2021.
http://hdl.handle.net/11343/36645.
MLA Handbook (7th Edition):
CAO, BENJAMIN. “Synthesis of immunogenic mycobacterial cell wall glycolipids.” 2011. Web. 17 Apr 2021.
Vancouver:
CAO B. Synthesis of immunogenic mycobacterial cell wall glycolipids. [Internet] [Doctoral dissertation]. University of Melbourne; 2011. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/11343/36645.
Council of Science Editors:
CAO B. Synthesis of immunogenic mycobacterial cell wall glycolipids. [Doctoral Dissertation]. University of Melbourne; 2011. Available from: http://hdl.handle.net/11343/36645
Wright State University
26.
Renick, Paul J.
CD28 Costimulation Requirement for Interferon-y Secretion by
Natural Killer T cells During Hepatitis B Virus Infection.
Degree: MS, Microbiology and Immunology, 2002, Wright State University
URL: http://rave.ohiolink.edu/etdc/view?acc_num=wright1040657636
► Renick, Paul James Rhodes. M.S. in Microbiology and Immunology, Wright State University. 2002. CD28 Costimulation Requirement for Interferon-y Secretion by Natural Killer T cells During…
(more)
▼ Renick, Paul James Rhodes. M.S. in Microbiology and
Immunology, Wright State University. 2002. CD28 Costimulation
Requirement for Interferon-y Secretion by Natural Killer T
cells
During Hepatitis B Virus Infection. Natural Killer T
cells (
NKT
cells) are a unique subset of lymphocytes that express natural
killer (NK) and T cell receptors (TCR). The
NKT cell population
includes four separate subclasses. This paper will focus on
Category I
NKT cells which possess a canonical TCR receptor
(Va14Ja281) that recognizes only hydrophobic antigens presented by
CD1d molecules. These
cells are believed to play an important
regulatory role in immunity. A variety of disease conditions,
including cancer, infections and Type I diabetes, are controlled by
NKT cells.
NKT cells are also capable of secreting large quantities
of cytokines, namely interleukin-4 (IL-4) and interferon-gamma
(IFN-y ). This ability to switch between Th1 (IFN-y ) and Th2
(IL-4) cytokines emphasizes the immunological regulatory role that
these
cells play. The mechanisms by which
NKT cells select the
cytokines they secrete are not well characterized. Blocking of CD28
by monoclonal antibodies or mutation of the CD28 gene impairs
NKT
cell s ability to secrete IFN-y in vitro.
NKT cell of IFN-y
secretion plays a significant role in the clearance of Hepatitis B
virus (HBV) in a HBV transgenic mouse model. Abrogating or blocking
expression of CD28 should significantly impair the ability of
NKT
cells to clear HBV infection. This thesis suggests a series of in
vitro and in vivo experiments designed to test the role of CD28 in
IFN-y secretion and HBV clearance in mice.
Advisors/Committee Members: Bigley, Nancy (Advisor).
Subjects/Keywords: Biology, Microbiology; CD28; NKT cells; HBV
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CSE |
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to Zotero / EndNote / Reference
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APA (6th Edition):
Renick, P. J. (2002). CD28 Costimulation Requirement for Interferon-y Secretion by
Natural Killer T cells During Hepatitis B Virus Infection. (Masters Thesis). Wright State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=wright1040657636
Chicago Manual of Style (16th Edition):
Renick, Paul J. “CD28 Costimulation Requirement for Interferon-y Secretion by
Natural Killer T cells During Hepatitis B Virus Infection.” 2002. Masters Thesis, Wright State University. Accessed April 17, 2021.
http://rave.ohiolink.edu/etdc/view?acc_num=wright1040657636.
MLA Handbook (7th Edition):
Renick, Paul J. “CD28 Costimulation Requirement for Interferon-y Secretion by
Natural Killer T cells During Hepatitis B Virus Infection.” 2002. Web. 17 Apr 2021.
Vancouver:
Renick PJ. CD28 Costimulation Requirement for Interferon-y Secretion by
Natural Killer T cells During Hepatitis B Virus Infection. [Internet] [Masters thesis]. Wright State University; 2002. [cited 2021 Apr 17].
Available from: http://rave.ohiolink.edu/etdc/view?acc_num=wright1040657636.
Council of Science Editors:
Renick PJ. CD28 Costimulation Requirement for Interferon-y Secretion by
Natural Killer T cells During Hepatitis B Virus Infection. [Masters Thesis]. Wright State University; 2002. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=wright1040657636
27.
Ghazarian, Liana.
Protection against type 1 diabetes upon Coxsackievirus B4 infection and iNKT cell stimulation : role of suppressive macrophages : Protection contre le diabète de type 1 par l’infection avec le virus de Coxsackie B4 et la stimulation des cellules TNK invariantes : le rôle des macrophages suppresseurs.
Degree: Docteur es, Immunologie, 2013, Université Paris Descartes – Paris V
URL: http://www.theses.fr/2013PA05T097
► Les cellules NKT invariantes (iNKT) sont des lymphocytes T non conventionnels restreints par la molécule CD1d qui présente des glycolipides. Les cellules iNKT expriment un…
(more)
▼ Les cellules
NKT invariantes (iNKT) sont des lymphocytes T non conventionnels restreints par la molécule CD1d qui présente des glycolipides. Les cellules iNKT expriment un TCR avec une chaîne a invariante, Va14-Ja18 chez la souris et Va28-Ja18 chez l’homme. Elles ont la particularité de produire de grande quantité de cytokines (IFN-? et IL-4) rapidement après leur activation et peuvent à leur tour stimuler d’autres cellules du système immunitaire comme les cellules dendritiques, les cellules NK et les lymphocytes T. Elles représentent ainsi un pont entre les réponses immunitaires innées et adaptatives. Le diabète de type 1 est une maladie autoimmune caractérisée par la destruction des cellules ß pancréatiques productrices d’insuline. Bien que l’apparition de diabète de type 1 soit associée à des polymorphismes génétiques, les facteurs environnementaux ont également été impliqués dans l’étiologie de cette maladie. De nombreuses études suggèrent que les infections virales, en particulier les infections par le virus de coxsackie B4 (CVB4), pourraient être impliquées dans le développement de cette maladie. Notre étude a été réalisée avec des souris NOD qui développent un diabète de type 1 vers 15 semaines d’âge et des souris NOD déficientes pour la proinsulin 2 (Pro-ins2-/-) développant un diabète vers 8 semaines d’âge. Nos résultats montrent qu’après infection par CVB4, la moitié des souris NOD et Pro-ins2-/- développent un diabète accéléré par rapport à des souris non infectées. Toutefois, une injection de l’agoniste des cellules iNKT, la molécule aGalactosylceramide (aGalCer), au moment de l’infection des souris, diminue fortement l’incidence de diabète. L’infection par CVB4 induit un fort recrutement de macrophages dans le pancréas et l’activation des cellules iNKT modifie la fonction de ces macrophages. En effet, les macrophages pancréatiques des souris infectées par CVB4 expriment fortement les cytokines IL-1ß, IL-6 et TNF-a, révélant leur caractère pro-inflammatoire alors que les macrophages des souris infectées et traitées par aGalCer expriment faiblement ces cytokines inflammatoires et fortement des enzymes immunosuppressives iNOS (inducible NO synthase), IDO (Indoleamine 2,3-dioxygenase) et arginase I. L’utilisation d’inhibiteurs de ces enzymes montre que la protection contre le diabète est induite par IDO. Nous avons également observé une forte infiltration de lymphocytes T autoréactifs dans les îlots pancréatiques des souris infectées. De façon intéressante, l’incidence accrue de diabète du groupe CVB4 est associée à une fréquence élevée de cellules T autoréactives produisant de l’IFN-? dans le pancréas, alors que la production d’IFN-? par les cellules T autoréactives est très faible dans les souris du groupe CVB4+aGalCer. Cette inhibition de la production d’IFN-? est dépendante de l’enzyme IDO, car l’utilisation d’un inhibiteur d’IDO augmente fortement la production d’IFN-? par les lymphocytes T anti-îlots et l’incidence de diabète. Dans l’ensemble nos résultats montrent, que l’activation des cellules iNKT…
Advisors/Committee Members: Lehuen, Agnès (thesis director).
Subjects/Keywords: Macrophages; Virus de coxsackie B4; Cellules NKT invariantes; Diabète de type 1; Macrophages; Coxsackievirus B4; Invariant NKT cells; Type 1 diabetes; 571.96
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APA ·
Chicago ·
MLA ·
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CSE |
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Manager
APA (6th Edition):
Ghazarian, L. (2013). Protection against type 1 diabetes upon Coxsackievirus B4 infection and iNKT cell stimulation : role of suppressive macrophages : Protection contre le diabète de type 1 par l’infection avec le virus de Coxsackie B4 et la stimulation des cellules TNK invariantes : le rôle des macrophages suppresseurs. (Doctoral Dissertation). Université Paris Descartes – Paris V. Retrieved from http://www.theses.fr/2013PA05T097
Chicago Manual of Style (16th Edition):
Ghazarian, Liana. “Protection against type 1 diabetes upon Coxsackievirus B4 infection and iNKT cell stimulation : role of suppressive macrophages : Protection contre le diabète de type 1 par l’infection avec le virus de Coxsackie B4 et la stimulation des cellules TNK invariantes : le rôle des macrophages suppresseurs.” 2013. Doctoral Dissertation, Université Paris Descartes – Paris V. Accessed April 17, 2021.
http://www.theses.fr/2013PA05T097.
MLA Handbook (7th Edition):
Ghazarian, Liana. “Protection against type 1 diabetes upon Coxsackievirus B4 infection and iNKT cell stimulation : role of suppressive macrophages : Protection contre le diabète de type 1 par l’infection avec le virus de Coxsackie B4 et la stimulation des cellules TNK invariantes : le rôle des macrophages suppresseurs.” 2013. Web. 17 Apr 2021.
Vancouver:
Ghazarian L. Protection against type 1 diabetes upon Coxsackievirus B4 infection and iNKT cell stimulation : role of suppressive macrophages : Protection contre le diabète de type 1 par l’infection avec le virus de Coxsackie B4 et la stimulation des cellules TNK invariantes : le rôle des macrophages suppresseurs. [Internet] [Doctoral dissertation]. Université Paris Descartes – Paris V; 2013. [cited 2021 Apr 17].
Available from: http://www.theses.fr/2013PA05T097.
Council of Science Editors:
Ghazarian L. Protection against type 1 diabetes upon Coxsackievirus B4 infection and iNKT cell stimulation : role of suppressive macrophages : Protection contre le diabète de type 1 par l’infection avec le virus de Coxsackie B4 et la stimulation des cellules TNK invariantes : le rôle des macrophages suppresseurs. [Doctoral Dissertation]. Université Paris Descartes – Paris V; 2013. Available from: http://www.theses.fr/2013PA05T097
Freie Universität Berlin
28.
Wricke, Katrin.
Contribution of lymphocytes to the pulmonary host defense response in mice
infected with Streptococcus pneumoniae.
Degree: 2013, Freie Universität Berlin
URL: http://dx.doi.org/10.17169/refubium-14447
► Pneumonia is the most prevalent infectious disease, and S. pneumoniae is the leading cause of community acquired pneumonia. The mechanisms of innate immunity in the…
(more)
▼ Pneumonia is the most prevalent infectious disease, and S. pneumoniae is the
leading cause of community acquired pneumonia. The mechanisms of innate
immunity in the lungs are incompletely understood. Particularly, the role of
NK-,
NKT- and T- lymphocytes in regulating innate defense of the lung remains
to be elucidated. For analysing the role of NK-,
NKT- and T- lymphocytes in
pneumonia, a mouse model of a severe pneumococcal pneumonia was developed.
Similar to humans, murine pneumonia was associated with infiltrates und
respiratory insufficiency. Furthermore, the mice showed signs of a peripheral
tissue hypoperfusion and hypotension. In addition to the clinical signs of
pneumonia and sepsis mice developed a local pulmonary, and consecutively
systemic, inflammatory immune response. During the course of infection,
neutrophils and monocytes were recruited into the lung. Staying at constant
levels during the first hours subsequent to infection, the number of
lymphocytes decreased after 48 hours. More specifically, the selective loss of
B- and CD4+-T- lymphocytes was observed. The number of CD8+-T- lymphocytes and
γδ-T-
cells remained constant, NK-
cells tended to increase, and
NKT-
cells
increased significantly. Furthermore, the NK- and
NKT- cell- activating
chemokines showed increased expression in the lung. NK- and
NKT-
cells were
rapidly activated and contributed significantly to the production of TNF and
IFN in the lung. Also, blood NK-
cells were activated and increased the
production of cytokines. In order to investigate the impact of NK/
NKT-
cells on
the course of pneumococcal pneumonia, these lymphocyte-subtypes were depleted.
The depletion of NK-
cells with Asialo-GM-antibody led to a reduction of
mortality. However, also the control-group, which received a polyclonal
immunoglobulin, showed a reduced mortality, suggesting a protective effectof
transfused IgM. The depletion of NK- and
NKT-
cells with anti-NK1.1-antibody
did not evoke significant mortality reduction. In conclusion, the current data
suggest an important function of NK- and
NKT-
cells in the course of
pneumococcal pneumonia. Further investigations using transgenic mice with
deficiency of lymphocyte subtypes for analysing the role of NK-,
NKT- and
T-
cells in the course of pneumococcal pneumonia are warranted.
Advisors/Committee Members: w (gender), Priv.-Doz. Dr. med. M. Witzenrath (firstReferee), Prof. Dr. med. T. Tschernig (furtherReferee), Prof. Dr. rer. nat. S. Hammerschmidt (furtherReferee).
Subjects/Keywords: pneumonia; S. pneumoniae; NK-cells; NKT-cells; lymphocytes; 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
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APA (6th Edition):
Wricke, K. (2013). Contribution of lymphocytes to the pulmonary host defense response in mice
infected with Streptococcus pneumoniae. (Thesis). Freie Universität Berlin. Retrieved from http://dx.doi.org/10.17169/refubium-14447
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Wricke, Katrin. “Contribution of lymphocytes to the pulmonary host defense response in mice
infected with Streptococcus pneumoniae.” 2013. Thesis, Freie Universität Berlin. Accessed April 17, 2021.
http://dx.doi.org/10.17169/refubium-14447.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Wricke, Katrin. “Contribution of lymphocytes to the pulmonary host defense response in mice
infected with Streptococcus pneumoniae.” 2013. Web. 17 Apr 2021.
Vancouver:
Wricke K. Contribution of lymphocytes to the pulmonary host defense response in mice
infected with Streptococcus pneumoniae. [Internet] [Thesis]. Freie Universität Berlin; 2013. [cited 2021 Apr 17].
Available from: http://dx.doi.org/10.17169/refubium-14447.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Wricke K. Contribution of lymphocytes to the pulmonary host defense response in mice
infected with Streptococcus pneumoniae. [Thesis]. Freie Universität Berlin; 2013. Available from: http://dx.doi.org/10.17169/refubium-14447
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Edinburgh
29.
Pattison, Mari Anne.
The effects of ageing on murine NKT cell and macrophage populations.
Degree: PhD, 2017, University of Edinburgh
URL: http://hdl.handle.net/1842/29559
► The immune system is a complex network of tissues, cells and proteins which protects us against infections and invading pathogens we encounter every day. Immunosenescence…
(more)
▼ The immune system is a complex network of tissues, cells and proteins which protects us against infections and invading pathogens we encounter every day. Immunosenescence refers to age-related impairments in immune function which may contribute to increased prevalence and severity of infectious disease in the elderly. How and why ageing affects the immune system is not fully understood. Using a naturally aged mouse model, work in this thesis shows that the abundance of a rare type of lymphocyte, known as NKT cells, increased across multiple immune organs. Additionally, macrophage abundance was also altered in the lymph nodes of aged mice. Invariant NKT (iNKT) cells express an invariant T cell receptor (TCR) which recognises lipids presented on the CD1d molecule. iNKT cells can be activated and respond to invading pathogens either by recognition of antigens through TCR-CD1d interactions or cytokine-dependent means. Less is known about NKT-like cells, which also express NK cell-associated surface markers, such as CD49b, but lack an invariant TCR. Data within this thesis show that both iNKT and NKT-like cell populations are abundant in the spleen and liver of aged mice. iNKT and NKT-like cells can be divided into subpopulations based on their expression of surface markers or transcription factors, and data suggests that not all subpopulations of these cells are affected by age equally. For instance, flow cytometry showed that while spleen-derived iNKT cells are significantly increased in aged mice, within the iNKT cell population the percentage representation of CD4+ cells are significantly reduced with age. Additionally, data indicates that both iNKT and NKT-like cells from aged mice show compromised responses to in vitro stimulation compared to young controls. Using bone marrow chimeras, where either young cells are reconstituted within an aged mouse or old cells are reconstituted within a young mouse, provided the opportunity to determine whether the aged environment contributes to this diminished response. Data demonstrates that the aged environment plays at least a partial role in these age-related changes to response to stimulation, however the young environment seems unable to reverse these changes. Macrophages are phagocytes which are found within all organs of the body. Studies in this thesis show that CD169+ macrophages have diminished numbers in the lymph nodes of aged mice, but this did not seem to affect the capture of the model antigen, dextran. Further studies revealed ageing affects macrophage populations differently in the different tissues within the body. For example, macrophage numbers remain constant in the spleen with ageing, but appear to increase in density in the lungs. To conclude, ageing can cause dramatic changes to the numbers and function of different cells of the immune system across multiple organs. Furthering our understanding of the ageing immune system and the underlying mechanisms which cause age-related decline in immune function is important to design strategies to improve the…
Subjects/Keywords: 616.07; mouse model; immunosenescence; NKT cells; T cell receptor; CD4+ cells; CD169+ macrophages; ageing immune systems; age-related decline
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APA ·
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MLA ·
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APA (6th Edition):
Pattison, M. A. (2017). The effects of ageing on murine NKT cell and macrophage populations. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/29559
Chicago Manual of Style (16th Edition):
Pattison, Mari Anne. “The effects of ageing on murine NKT cell and macrophage populations.” 2017. Doctoral Dissertation, University of Edinburgh. Accessed April 17, 2021.
http://hdl.handle.net/1842/29559.
MLA Handbook (7th Edition):
Pattison, Mari Anne. “The effects of ageing on murine NKT cell and macrophage populations.” 2017. Web. 17 Apr 2021.
Vancouver:
Pattison MA. The effects of ageing on murine NKT cell and macrophage populations. [Internet] [Doctoral dissertation]. University of Edinburgh; 2017. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/1842/29559.
Council of Science Editors:
Pattison MA. The effects of ageing on murine NKT cell and macrophage populations. [Doctoral Dissertation]. University of Edinburgh; 2017. Available from: http://hdl.handle.net/1842/29559
University of Melbourne
30.
Fong, Shao Bing.
Characterisation of innate T cells in response to oral bacterial infection.
Degree: 2015, University of Melbourne
URL: http://hdl.handle.net/11343/91554
► Chronic periodontitis is an inflammatory disease of the supporting tissues of teeth that is characterised by bone resorption and if left untreated can result in…
(more)
▼ Chronic periodontitis is an inflammatory disease of the supporting tissues of teeth that is characterised by bone resorption and if left untreated can result in eventual tooth loss. The subgingival plaque bacteria Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia have been closely associated with chronic periodontitis. T cell immunity during periodontal infections has been well-documented, mainly involving the adaptive immunity which includes Th1 and Th2 responses. A small number of clinical studies have reported the presence of IL-17 and Th17-related cytokines in the gingival crevicular fluid and diseased tissues of periodontitis patients. However, the roles of innate T cells and Th17-related responses in disease progression is unclear.
This study shows that NKT cells play a role in pro-inflammatory cytokine production, contributing to P. gingivalis-induced bone loss in the mouse periodontitis model. Inflammation and bone resorption was reduced in the absence of NKT cells or CD1d, the corresponding activating receptor for the TCR of NKT cells. As NKT cell responses were likely to be associated with glycolipid antigens, a major glycolipid of P. gingivalis was isolated, Pg-GL1, which was found to induce NKT cell and B cell activation. Results from knock-out mice studies suggested that NKT activation by Pg-GL1 occurs through a mixed requirement for TCR/CD1d-engagement and additional cytokines. Furthermore, Pg-GL1 was shown to induce the secretion of IL-1β, IL-6, IL-12(p40), IL-17, and G-CSF, cytokines that have been associated with inducing Th17-responses and, as contributing factors during periodontal inflammation and bone resorption.
Similar to P. gingivalis, three major glycolipids (termed Tf-GL1, Tf-GL2, Tf-GL3) of T. forsythia were found to highly activate NKT cells and B cells. Alkaline treatment of T. forsythia glycolipids revealed that Tf-GL2 was alkali-resistant, while Tf-GL1 and Tf-GL3 were susceptible and their deacylated forms showed the presence of complex carbohydrates. Mass spectrometry analysis revealed a wide structural variation in the carbohydrate head-group and acyl chain lengths. Base-labile Tf-GL1 and Tf-GL3 were identified to be diacylgylcerolipids while base-resistant Tf-GL2 was proposed to be a glycosphingolipid. The structure of the third glycolipid, Tf-GL3, was predicted to be highly complex and thus may have contributed to its lower antigenicity compared with Tf-GL1 and Tf-GL2. When the stimulatory ability of T. forsythia glycolipids was further investigated, only Tf-GL2 was able to induce IL-17 production when cultured with purified NKT cells and BMDCs. As only Tf-GL2 was able to induce cytokine production, it was concluded that structural characteristics play an important role in antigen potency.
When mice were orally infected with P. gingivalis, the CD27- γδ T cell sub-population in the maxillary epithelium was found to be activated after 14 days post-infection. Using pHrodo™ technology, it was shown that γδ T cells were able to phagocytose…
Subjects/Keywords: immunology; microbiology; innate immunity; NKT cells; gamma-delta T cells; periodontitis; glycolipids; porphyromonas gingivalis; Tannerella forsythia; oral bacteria; cytokines
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Record Details
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Fong, S. B. (2015). Characterisation of innate T cells in response to oral bacterial infection. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/91554
Chicago Manual of Style (16th Edition):
Fong, Shao Bing. “Characterisation of innate T cells in response to oral bacterial infection.” 2015. Doctoral Dissertation, University of Melbourne. Accessed April 17, 2021.
http://hdl.handle.net/11343/91554.
MLA Handbook (7th Edition):
Fong, Shao Bing. “Characterisation of innate T cells in response to oral bacterial infection.” 2015. Web. 17 Apr 2021.
Vancouver:
Fong SB. Characterisation of innate T cells in response to oral bacterial infection. [Internet] [Doctoral dissertation]. University of Melbourne; 2015. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/11343/91554.
Council of Science Editors:
Fong SB. Characterisation of innate T cells in response to oral bacterial infection. [Doctoral Dissertation]. University of Melbourne; 2015. Available from: http://hdl.handle.net/11343/91554
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Open Access Theses and Dissertations
