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International Immunology Advance Access published online on December 23, 2008
International Immunology, doi:10.1093/intimm/dxn136
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© The Japanese Society for Immunology. 2008. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Altered production of immunoregulatory cytokines by invariant V{alpha}19 TCR-bearing cells dependent on the duration and intensity of TCR engagement

Michio Shimamura1,2, Yi-Ying Huang1, Masumi Kobayashi1 and Hiroshi Goji1

1 Developmental Immunology Unit, Mitsubishi Kagaku Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan
2 Department of Immunology, National Institute of Neurosciences, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashimachi, Kodaira, Tokyo 187-8502, Japan

Correspondence to: Correspondence to: M. Shimamura; E-mail: michio{at}libra.ls.m-kagaku.co.jp

Cells bearing invariant V{alpha}19-J{alpha}33 TCR {alpha} chains are believed to participate in the regulation of inflammatory autoimmune diseases. In this study, the potential to produce immunoregulatory cytokines by these cells was characterized in order to find the mechanism underlying their immunoregulatory functions. Serum levels of IL-4, IL-10, transforming growth factor-β, IFN-{gamma} and IL-17 increased in mice over-expressing an invariant V{alpha}19-J{alpha}33 TCR {alpha} transgene (V{alpha}19 Tg) in response to anti-CD3 antibody injection. NK1.1+ V{alpha}19 Tg+, but not NK1.1– V{alpha}19 Tg+ cells, promptly produced immunoregulatory IL-4, IFN-{gamma} and IL-17 upon invariant TCR engagement with immobilized anti-CD3 antibody in culture. The activation of V{alpha}19 Tg+ cells then triggered the production of pro-inflammatory cytokines by bystander cells. Interestingly, the ratio of Th2 cytokines such as IL-4, IL-5 and IL-10, but not pro-inflammatory IL-17, to IFN-{gamma} was increased when the intensity of the stimulation to invariant TCR was attenuated. Collectively, these findings suggest that invariant V{alpha}19 TCR+ cells have the potential to participate in the regulation of inflammatory autoimmunity by producing Th2-biased cytokines in certain circumstances.

Keywords: cytokine, immunoregulation, invariant TCR, NKT cell

Transmitting editor: G. Trinchieri

Received 28 July 2008, accepted 26 November 2008.


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