Shimamura Michio, Huang Yi-Ying, Kobayashi Masumi, Goji Hiroshi
Developmental Immunology Unit, Mitsubishi Kagaku Institute of Life Sciences, Machida, Tokyo, Japan.
Int Immunol. 2009 Feb;21(2):179-85. doi: 10.1093/intimm/dxn136. Epub 2008 Dec 23.
Cells bearing invariant Valpha19-Jalpha33 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 Valpha19-Jalpha33 TCR alpha transgene (Valpha19 Tg) in response to anti-CD3 antibody injection. NK1.1(+) Valpha19 Tg(+), but not NK1.1(-) Valpha19 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 Valpha19 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 Valpha19 TCR(+) cells have the potential to participate in the regulation of inflammatory autoimmunity by producing T(h)2-biased cytokines in certain circumstances.
携带恒定的Vα19-Jα33 TCR α链的细胞被认为参与炎症性自身免疫疾病的调节。在本研究中，对这些细胞产生免疫调节细胞因子的潜力进行了表征，以探寻其免疫调节功能的潜在机制。在注射抗CD3抗体后，过表达恒定Vα19-Jα33 TCR α转基因（Vα19 Tg）的小鼠血清中IL-4、IL-10、转化生长因子-β、IFN-γ和IL-17水平升高。在培养中，当恒定TCR与固定的抗CD3抗体结合时，NK1.1(+) Vα19 Tg(+)细胞（而非NK1.1(-) Vα19 Tg(+)细胞）迅速产生免疫调节性IL-4、IFN-γ和IL-17。Vα19 Tg(+)细胞的激活随后引发旁邻细胞产生促炎细胞因子。有趣的是，当对恒定TCR的刺激强度减弱时，IL-4、IL-5和IL-10等Th2细胞因子与IFN-γ的比例增加，但促炎细胞因子IL-17与IFN-γ的比例未增加。总体而言，这些发现表明，恒定Vα19 TCR(+)细胞在某些情况下具有通过产生偏向Th2的细胞因子参与炎症性自身免疫调节的潜力。
