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Natural killer T cell subsets and regulation of autoimmune diabetes

Stenström, Martin LU (2005)
Abstract
This thesis is focused on natural killer (NK) T cells. NKT cells recognize lipids and glycolipids, rather than peptides, in the contents of the antigen presenting molecule CD1d. NKT cells have a surface phenotype reminiscent of memory cells, and have been shown to rapidly produce large amounts of cytokines, such as IL-4 and IFN-gamma, upon activation. Because of their rapid response to activation, NKT cells have been suggested to play a role in several different immunological situations, such as clearance of pathogens, tumor rejection and regulation of autoimmune reactions. The broad spectrum of their activities suggested that functionally different subsets of NKT cells might exist. We have been able to demonstrate two functionally... (More)
This thesis is focused on natural killer (NK) T cells. NKT cells recognize lipids and glycolipids, rather than peptides, in the contents of the antigen presenting molecule CD1d. NKT cells have a surface phenotype reminiscent of memory cells, and have been shown to rapidly produce large amounts of cytokines, such as IL-4 and IFN-gamma, upon activation. Because of their rapid response to activation, NKT cells have been suggested to play a role in several different immunological situations, such as clearance of pathogens, tumor rejection and regulation of autoimmune reactions. The broad spectrum of their activities suggested that functionally different subsets of NKT cells might exist. We have been able to demonstrate two functionally distinct splenic NKT cell populations identified by their surface phenotype and cytokine secretion profile. Previous reports of reduced autoimmune diabetes incidence in NOD mice related to an artificially increased NKT cell population have been attributed to the enhanced production of IL-4 by classical NKT cells. We show that an overexpression in NOD mice of non-classical NKT cells, producing high levels of IFN-gamma but low amounts of IL-4, leads to prevention of autoimmune diabetes. This demonstrates that both classical and non-classical NKT cells possess immuno-regulatory functions. Finding out which mechanisms that are shared by all NKT cells and which that are not, will broaden our knowledge on NKT cell biology and increase the possibility to control the immune system in a way that may prevent diseases and autoimmunity. (Less)
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author
supervisor
opponent
  • Dr Dellabona, Paolo, San Raffaele Scientific Institute, Milano, Italy
organization
publishing date
type
Thesis
publication status
published
subject
keywords
serology, transplantation, CD1d, NKT cells, Immunology, autoimmune diabetes, serologi, Immunologi
pages
122 pages
publisher
Lund University (Media-Tryck)
defense location
GK-salen, BMC, Sölvegatan 19, Lund.
defense date
2005-12-15 09:00:00
ISBN
91-85481-23-8
language
English
LU publication?
yes
additional info
M Stenström, M Sköld, A Ericsson, L Beaudoin, S Sidobre, M Kronenberg, A Lehuen and S Cardell. 2004. Surface receptors identify mouse NK1.1+ T cell subsets distinguished by function and T cell receptor type. Eur. J. Immunol., vol 34 pp 56-65.
M Stenström, M Sköld, Å Andersson and S L Cardell. 2005. Natural killer T-cell populations in C57BL/6 and NK1.1 congenic BALB.NK mice – a novel thymic subset defined in BALB.NK mice. Immunology, vol 114 pp 336-345.
N Duarte, M Stenström, S Campino, M-L Bergman, M Lundholm, D Holmberg and S L Cardell. 2004. Prevention of diabetes in nonobese diabetic mice mediated by CD1d-restricted nonclassical NKT cells. J. Immunol., vol 173 pp 3112-3118.
id
81dd6e92-bd05-47bf-bbf3-62bca44bbb72 (old id 545937)
date added to LUP
2016-04-01 16:17:36
date last changed
2018-11-21 20:40:14
@phdthesis{81dd6e92-bd05-47bf-bbf3-62bca44bbb72,
  abstract     = {{This thesis is focused on natural killer (NK) T cells. NKT cells recognize lipids and glycolipids, rather than peptides, in the contents of the antigen presenting molecule CD1d. NKT cells have a surface phenotype reminiscent of memory cells, and have been shown to rapidly produce large amounts of cytokines, such as IL-4 and IFN-gamma, upon activation. Because of their rapid response to activation, NKT cells have been suggested to play a role in several different immunological situations, such as clearance of pathogens, tumor rejection and regulation of autoimmune reactions. The broad spectrum of their activities suggested that functionally different subsets of NKT cells might exist. We have been able to demonstrate two functionally distinct splenic NKT cell populations identified by their surface phenotype and cytokine secretion profile. Previous reports of reduced autoimmune diabetes incidence in NOD mice related to an artificially increased NKT cell population have been attributed to the enhanced production of IL-4 by classical NKT cells. We show that an overexpression in NOD mice of non-classical NKT cells, producing high levels of IFN-gamma but low amounts of IL-4, leads to prevention of autoimmune diabetes. This demonstrates that both classical and non-classical NKT cells possess immuno-regulatory functions. Finding out which mechanisms that are shared by all NKT cells and which that are not, will broaden our knowledge on NKT cell biology and increase the possibility to control the immune system in a way that may prevent diseases and autoimmunity.}},
  author       = {{Stenström, Martin}},
  isbn         = {{91-85481-23-8}},
  keywords     = {{serology; transplantation; CD1d; NKT cells; Immunology; autoimmune diabetes; serologi; Immunologi}},
  language     = {{eng}},
  publisher    = {{Lund University (Media-Tryck)}},
  school       = {{Lund University}},
  title        = {{Natural killer T cell subsets and regulation of autoimmune diabetes}},
  url          = {{https://lup.lub.lu.se/search/files/4628387/545938.pdf}},
  year         = {{2005}},
}