Abstract
T cells expressing an invariant V(alpha)19-J(alpha)33 T cell receptor alpha-chain (V(alpha)19i TCR) are restricted by the nonpolymorphic major histocompatibility complex class Ib molecule MR1. Whether V(alpha)19i T cells are involved in autoimmunity is not understood. Here we demonstrate that T cells expressing the V(alpha)19i TCR transgene inhibited the induction and progression of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Similarly, EAE was exacerbated in MR1-deficient mice, which lack V(alpha)19i T cells. EAE suppression was accompanied by reduced production of inflammatory mediators and increased secretion of interleukin 10. Interleukin 10 production occurred at least in part through interactions between B cells and V(alpha)19i T cells mediated by the ICOS costimulatory molecule. These results suggest an immunoregulatory function for V(alpha)19i T cells.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antigens, CD1 / genetics
-
Antigens, CD1d
-
Antigens, Differentiation, T-Lymphocyte / pharmacology
-
B-Lymphocytes / immunology
-
Encephalomyelitis, Autoimmune, Experimental / immunology*
-
Histocompatibility Antigens Class I / genetics
-
Immunoglobulin Variable Region / analysis
-
Immunoglobulin Variable Region / genetics
-
Inducible T-Cell Co-Stimulator Protein
-
Interleukin-10 / metabolism
-
Lymphocyte Activation
-
Mice
-
Mice, Transgenic
-
Minor Histocompatibility Antigens
-
Multiple Sclerosis / immunology*
-
Receptors, Antigen, T-Cell, alpha-beta / analysis*
-
Receptors, Antigen, T-Cell, alpha-beta / genetics
-
T-Lymphocytes, Regulatory / drug effects
-
T-Lymphocytes, Regulatory / immunology*
Substances
-
Antigens, CD1
-
Antigens, CD1d
-
Antigens, Differentiation, T-Lymphocyte
-
Histocompatibility Antigens Class I
-
Icos protein, mouse
-
Immunoglobulin Variable Region
-
Inducible T-Cell Co-Stimulator Protein
-
Minor Histocompatibility Antigens
-
Mr1 protein, mouse
-
Receptors, Antigen, T-Cell, alpha-beta
-
Interleukin-10