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|Title||Natural killer T cell subsets and regulation of autoimmune diabetes|
|Full-text||Available as PDF|
|Defence place||GK-salen, BMC, Sölvegatan 19, Lund.|
|Opponent||Dr Paolo Dellabona|
|Abstract English||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.|
Medicine and Health Sciences
|Keywords||transplantation, serology, CD1d, NKT cells, Immunology, autoimmune diabetes, serologi, Immunologi|
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.