刚刚在线出版的Nature系列杂志Cell death & differentiation报道了复旦大学医学院王缨教授和熊思东教授的重要研究成果，发现CD4+CD25+调节性T细胞（Treg）的免疫抑制机制与tumor necrosis factor-related apoptosis inducing ligand (TRAIL)/death receptor 5 (DR5)信号通路密切相关，在体和离体都显示这一现象。这一研究成果为提高移植免疫存活期提供了重要的参考，也为未来开发有效的免疫抑制药物提供有价值的靶点。

　　王缨和熊思东教授在2006年的研究中观察到FasL/Fas及其他凋亡相关分子可能参与了CD4＋CD25＋调节性T细胞的凋亡，这一研究成果在此基础上进一步明确的TRAIL/DR5信号通路的机制。

免费全文下载

原始文献：

Involvement of cellular death in TRAIL/DR5-dependent suppression induced by CD4⁺CD25⁺ regulatory T cells FREE

X Ren, F Ye, Z Jiang, Y Chu, S Xiong and Y Wang

Cell Death Differ 14: 2076-2084; advance online publication, August 31, 2007; doi:10.1038/sj.cdd.4402220

Abstract|Full Text|PDF|Supplementary information

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⁺ Tregin 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 Tregin vitro. Activated Treg displayed TRAIL-dependent cytotoxicity against CD4⁺ T cellsin 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 bothin vitroandin vivo.

                                                       摘自《生物谷》