Altered production of immunoregulatory cytokines by invariant Vα19 TCR-bearing cells dependent on the duration and intensity of TCR engagement

Cells bearing invariant Va19-Ja33 TCR a 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-b, IFN-g and IL-17 increased in mice over-expressing an invariant Va19-Ja33 TCR a transgene (Va19 Tg) in response to anti-CD3 antibody injection. NK1.1 1 Va19 Tg 1 , but not NK1.1 2 Va19 Tg 1 cells, promptly produced immunoregulatory IL-4, IFN-g and IL-17 upon invariant TCR engagement with immobilized anti-CD3 antibody in culture. The activation of Va19 Tg 1 cells then triggered the production of proinflammatory 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-g was increased when the intensity of the stimulation to invariant TCR was attenuated. Collectively, these findings suggest that invariant Va19 TCR 1 cells have the potential to participate in the regulation of inflammatory autoimmunity by producing Th2biased cytokines in certain circumstances.