Ring Sabine, Schäfer Stephan C, Mahnke Karsten, Lehr Hans-Anton, Enk Alexander H
Department of Dermatology, University of Heidelberg, Heidelberg, Germany.
Eur J Immunol. 2006 Nov;36(11):2981-92. doi: 10.1002/eji.200636207.
CD4+ CD25+ regulatory T cells (Treg) exert suppressive functions on effector T cells in vitro and in vivo. However, the exact cellular events that mediate this inhibitory action remain largely unclear. To elucidate these events, we used intravital microscopy in a model of contact hypersensitivity (CHS) and visualized the leukocyte-endothelium interaction at the site of antigen challenge in awake C57BL/6 mice. Injection of Treg i.v. into sensitized mice at the time of local hapten challenge significantly inhibited rolling and adhesion of endogenous leukocytes to the endothelium. A similar inhibition of leukocyte recruitment could be recorded after injection of Treg-derived tissue culture supernatant. Thus, these data indicate that soluble factors may account for the suppressive effects. Accordingly we found that IL-10, but not TGF-beta, was produced by Treg upon stimulation and that addition of anti-IL-10 antibodies abrogated the suppressive effects of Treg and tissue culture supernatant in CHS reactions. Moreover, CD4+ CD25+ T cells isolated from IL-10-/- mice were not able to suppress the immune response induced by hapten treatment in C57BL/6 mice. In conclusion, our data suggest that cytokine-dependent rather than cell-cell contact-dependent mechanisms play a pivotal role in the suppression of CHS reactions by Treg in vivo.
CD4+ CD25+调节性T细胞（Treg）在体外和体内对效应T细胞发挥抑制功能。然而，介导这种抑制作用的确切细胞事件在很大程度上仍不清楚。为了阐明这些事件，我们在接触性超敏反应（CHS）模型中使用了活体显微镜，并在清醒的C57BL/6小鼠抗原攻击部位观察白细胞与内皮细胞的相互作用。在局部半抗原攻击时静脉注射Treg到致敏小鼠体内，可显著抑制内源性白细胞在内皮细胞上的滚动和黏附。注射Treg来源的组织培养上清液后，也可记录到对白细胞募集的类似抑制作用。因此，这些数据表明可溶性因子可能是抑制作用的原因。相应地，我们发现Treg在受到刺激时产生IL-10，而不是TGF-β，并且添加抗IL-10抗体可消除Treg和组织培养上清液在CHS反应中的抑制作用。此外，从IL-10基因敲除小鼠中分离的CD4+ CD25+ T细胞无法抑制C57BL/6小鼠中半抗原处理诱导的免疫反应。总之，我们的数据表明，细胞因子依赖性而非细胞间接触依赖性机制在体内Treg对CHS反应的抑制中起关键作用。
