1Université Pierre et Marie Curie -- Univ Paris 06, France.
J Clin Invest. 2010 Dec;120(12):4558-68. doi: 10.1172/JCI42945. Epub 2010 Nov 22.
CD4+CD25+Foxp3+ Tregs play a major role in prevention of autoimmune diseases. The suppressive effect of Tregs on effector T cells (Teffs), the cells that can mediate autoimmunity, has been extensively studied. However, the in vivo impact of Teff activation on Tregs during autoimmunity has not been explored. In this study, we have shown that CD4+ Teff activation strongly boosts the expansion and suppressive activity of Tregs. This helper function of CD4+ T cells, which we believe to be novel, was observed in the pancreas and draining lymph nodes in mouse recipients of islet-specific Teffs and Tregs. Its physiological impact was assessed in autoimmune diabetes. When islet-specific Teffs were transferred alone, they induced diabetes. Paradoxically, when the same Teffs were cotransferred with islet-specific Tregs, they induced disease protection by boosting Treg expansion and suppressive function. RNA microarray analyses suggested that TNF family members were involved in the Teff-mediated Treg boost. In vivo experiments showed that this Treg boost was partially dependent on TNF but not on IL-2. This feedback regulatory loop between Teffs and Tregs may be critical to preventing or limiting the development of autoimmune diseases.
CD4+CD25+Foxp3+Tregs 在预防自身免疫性疾病中发挥重要作用。Tregs 对效应 T 细胞（Teffs）的抑制作用，即能够介导自身免疫的细胞，已得到广泛研究。然而，Teff 活化在自身免疫过程中对 Tregs 的体内影响尚未得到探索。在本研究中，我们表明 CD4+Teff 活化强烈促进了 Tregs 的扩增和抑制活性。我们认为这种 CD4+T 细胞的辅助功能是新颖的，在胰岛特异性 Teffs 和 Tregs 小鼠受体内的胰腺和引流淋巴结中观察到了这种功能。在自身免疫性糖尿病中评估了其生理影响。当单独转导胰岛特异性 Teffs 时，它们会引发糖尿病。矛盾的是，当相同的 Teffs 与胰岛特异性 Tregs 共转导时，它们通过促进 Treg 扩增和抑制功能诱导疾病保护。RNA 微阵列分析表明 TNF 家族成员参与了 Teff 介导的 Treg 扩增。体内实验表明，这种 Treg 扩增部分依赖于 TNF，但不依赖于 IL-2。Teffs 和 Tregs 之间的这种反馈调节环可能对预防或限制自身免疫性疾病的发展至关重要。
