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Publication : Invariant NKT cells exacerbate type 1 diabetes induced by CD8 T cells.

First Author  Griseri T Year  2005
Journal  J Immunol Volume  175
Issue  4 Pages  2091-101
PubMed ID  16081775 Mgi Jnum  J:107517
Mgi Id  MGI:3621347 Doi  10.4049/jimmunol.175.4.2091
Citation  Griseri T, et al. (2005) Invariant NKT cells exacerbate type 1 diabetes induced by CD8 T cells. J Immunol 175(4):2091-101
abstractText  Invariant NKT (iNKT) cells have been implicated in the regulation of autoimmune diseases. In several models of type 1 diabetes, increasing the number of iNKT cells prevents the development of disease. Because CD8 T cells play a crucial role in the pathogenesis of diabetes, we have investigated the influence of iNKT cells on diabetogenic CD8 T cells. In the present study, type 1 diabetes was induced by the transfer of CD8 T cells specific for the influenza virus hemagglutinin into recipient mice expressing the hemagglutinin Ag specifically in their beta pancreatic cells. In contrast to previous reports, high frequency of iNKT cells promoted severe insulitis and exacerbated diabetes. Analysis of diabetogenic CD8 T cells showed that iNKT cells enhance their activation, their expansion, and their differentiation into effector cells producing IFN-gamma. This first analysis of the influence of iNKT cells on diabetogenic CD8 T cells reveals that iNKT cells not only fail to regulate but in fact exacerbate the development of diabetes. Thus, iNKT cells can induce opposing effects dependent on the model of type 1 diabetes that is being studied. This prodiabetogenic capacity of iNKT cells should be taken into consideration when developing therapeutic approaches based on iNKT cell manipulation.
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