Ren X, Ye F, Jiang Z, Chu Y, Xiong S, Wang Y
Institute for Immunobiology and Department of Immunology, Shanghai Medical College, Fudan University, Shanghai, China.
Cell Death Differ. 2007 Dec;14(12):2076-84. doi: 10.1038/sj.cdd.4402220. Epub 2007 Aug 31.
CD4(+)CD25(+) regulatory T cells (Treg) are potent immunosuppressive cells active in controlling normal pathological immune responses. The mechanisms of this suppression have been investigated under various conditions. In this report, tumor necrosis factor-related apoptosis inducing ligand (TRAIL)/death receptor 5 (DR5) was explored as one of the pivotal factors for the suppression and cytotoxicity induced by CD4(+)CD25(+) Treg. Cell death was involved in the suppression induced by activated CD4(+)CD25(+) Treg in vitro. The induction of CD4(+) T cell death was not mediated by the CD95/CD95L pathway, but rather depended upon the upregulation of TRAIL in the Treg. Blocking the TRAIL/DR5 pathway resulted in a significant reduction of the suppressive activity as well as the cytotoxic effects of Treg in vitro. Activated Treg displayed TRAIL-dependent cytotoxicity against CD4(+) T cells in vivo. The prolonged survival of allogeneic skin grafts induced by Treg was inhibited by DR5-blocking antibodies. Our findings suggest that the TRAIL/DR5 pathway is one of the mechanisms used by Treg to regulate immune responses both in vitro and in vivo.
CD4(+)CD25(+)调节性T细胞（Treg）是在控制正常病理免疫反应中起作用的强效免疫抑制细胞。这种抑制的机制已在各种条件下进行了研究。在本报告中，肿瘤坏死因子相关凋亡诱导配体（TRAIL）/死亡受体5（DR5）被探索为CD4(+)CD25(+) Treg诱导抑制和细胞毒性的关键因素之一。细胞死亡参与了体外活化的CD4(+)CD25(+) Treg诱导的抑制作用。CD4(+) T细胞死亡的诱导不是由CD95/CD95L途径介导的，而是依赖于Treg中TRAIL的上调。阻断TRAIL/DR5途径导致体外Treg的抑制活性以及细胞毒性作用显著降低。活化的Treg在体内对CD4(+) T细胞表现出TRAIL依赖性细胞毒性。Treg诱导的同种异体皮肤移植物的长期存活受到DR5阻断抗体的抑制。我们的研究结果表明，TRAIL/DR5途径是Treg在体外和体内调节免疫反应所使用的机制之一。
