Invariant V(alpha)19i T cells regulate autoimmune inflammation.
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.
Croxford
J Ludovic
JL
Department of Immunology, National Institute of Neuroscience, National Centre of Neurology and Psychiatry, Tokyo 187-8502, Japan.
Miyake
Sachiko
S
Huang
Yi-Ying
YY
Shimamura
Michio
M
Yamamura
Takashi
T
D000818:Animals; D018949:Antigens, CD1 / Q000235:genetics; D055610:Antigens, CD1d; D000945:Antigens, Differentiation, T-Lymphocyte / Q000494:pharmacology; D001402:B-Lymphocytes / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000032:analysis / Q000235:genetics; D060889:Inducible T-Cell Co-Stimulator Protein; D016753:Interleukin-10 / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D015778:Minor Histocompatibility Antigens; D009103:Multiple Sclerosis / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis* / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*
D018949:Antigens, CD1; D055610:Antigens, CD1d; D000945:Antigens, Differentiation, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; C556694:Icos protein, mouse; D007135:Immunoglobulin Variable Region; D060889:Inducible T-Cell Co-Stimulator Protein; D015778:Minor Histocompatibility Antigens; C490628:Mr1 protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016753:Interleukin-10