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Publication : NK T cell-derived IL-10 is essential for the differentiation of antigen-specific T regulatory cells in systemic tolerance.

First Author  Sonoda KH Year  2001
Journal  J Immunol Volume  166
Issue  1 Pages  42-50
PubMed ID  11123275 Mgi Jnum  J:125981
Mgi Id  MGI:3760324 Doi  10.4049/jimmunol.166.1.42
Citation  Sonoda KH, et al. (2001) NK T cell-derived IL-10 is essential for the differentiation of antigen-specific T regulatory cells in systemic tolerance. J Immunol 166(1):42-50
abstractText  In a model of systemic tolerance called Anterior Chamber-Associated Immune Deviation (ACAID), the differentiation of the T regulatory (Tr) cells depends on NK T cells and occurs in the spleen. We now show that the CD1d-reactive NK T cell subpopulation, required for development of systemic tolerance, expresses the invariant V alpha 14J alpha 281 TCR because J alpha 281 knockout (KO) mice were unable to generate Ag-specific Tr cells and ACAID. The mechanism for NK T cell-dependent differentiation of Ag-specific Tr cells mediating systemic tolerance was studied by defining the cytokine profiles in heterogeneous and enriched NK T spleen cells. In contrast to there being no differences in most regulatory cytokine mRNAs, both mRNA and protein for IL-10 were increased in splenic NK T cells of anterior chamber (a.c.)-inoculated mice. However, IL-10 mRNA was not increased in spleens after i.v. inoculation. Finally, NK T cells from wild-type (WT) mice, but not from IL-10 KO mice, reconstituted the ACAID inducing ability in J alpha 281 KO mice. Thus, NK T cell-derived IL-10 is critical for the generation of the Ag-specific Tr cells and systemic tolerance induced to eye-inoculated Ags.
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