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Invariant Vα19i T cells regulate autoimmune inflammation

Nature Immunology volume 7, pages 987994 (2006) | Download Citation

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Abstract

T cells expressing an invariant Vα19-Jα33 T cell receptor α-chain (Vα19i TCR) are restricted by the nonpolymorphic major histocompatibility complex class Ib molecule MR1. Whether Vα19i T cells are involved in autoimmunity is not understood. Here we demonstrate that T cells expressing the Vα19i 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 Vα19i 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 Vα19i T cells mediated by the ICOS costimulatory molecule. These results suggest an immunoregulatory function for Vα19i T cells.

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Acknowledgements

We thank S. Gilfillan (Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri) for Mr1−/− mice. Supported by the Japan Society for the Promotion of Science (P03581 to J.L.C), the Ministry of Health, Labour and Welfare of Japan (T.Y. and S.M.), The Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (02-5 to T.Y.), Grant-in-Aid for Science Research on Priority Area from Ministry of Education, Science, Sports and Culture of Japan (17047051 to S.M.) and Grant-in-Aid for Scientific Research (B) (18390295 to S.M.) from the Japan Society for the Promotion of Science.

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Affiliations

  1. Department of Immunology, National Institute of Neuroscience, National Centre of Neurology and Psychiatry, Tokyo 187-8502, Japan.

    • J Ludovic Croxford
    • , Sachiko Miyake
    •  & Takashi Yamamura
  2. Developmental Immunology Unit, Mitsubishi Kagaku Institute of Life Sciences, Tokyo 194-8511, Japan.

    • Yi-Ying Huang
    •  & Michio Shimamura

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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Takashi Yamamura.

Supplementary information

PDF files

  1. 1.

    Supplementary Fig. 1

    Expression of adhesion molecules on the surface of TCRβ+ T cells from Vα19iTgCd1d−/− mice is inhibited during EAE.

  2. 2.

    Supplementary Fig. 2

    MOG35-55 peptide enhances Vα19i T cell-mediated IL-10 production.

  3. 3.

    Supplementary Table 1

    Table shows primer gene names and sequences (5′ to 3′) used in this paper for real-time RT-PCR.

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DOI

https://doi.org/10.1038/ni1370

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