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

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-beta, 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 T(h)2 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 T(h)2-biased cytokines in certain circumstances.