Human regulatory T cells induce T-lymphocyte senescence.
Human regulatory T cells induce T-lymphocyte senescence.
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DOI：
10.1182/blood-2012-03-416040
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发表时间：
2012-09
期刊：
影响因子：
20.3
通讯作者：
Jian Ye;Xingxu Huang;E. Hsueh;Qunyuan Zhang;Chunling Ma;Yanping Zhang;M. Varvares;D. Hoft;Guangyong Peng
中科院分区：
文献类型：
--
作者：
Jian Ye;Xingxu Huang;E. Hsueh;Qunyuan Zhang;Chunling Ma;Yanping Zhang;M. Varvares;D. Hoft;Guangyong Peng
调节性T（Treg）细胞对宿主免疫具有广泛的抑制活性，但受抑制的应答性T细胞的命运和功能在很大程度上仍然未知。在本研究中，我们报告了人Treg细胞可以在体外和体内诱导应答者幼稚和效应T细胞的衰老。由人Treg细胞诱导的衰老应答T细胞改变了它们的表型和细胞因子谱，并且具有强的抑制功能。此外，Treg介导的应答T细胞衰老的分子控制与p38和ERK 1/2信号传导以及细胞周期调节分子p16、p21和p53的选择性调节相关。我们进一步揭示了人Treg诱导的衰老和抑制功能可以通过TLR 8信号传导和/或通过特异性ERK 1/2和p38抑制在体外和体内动物模型中被阻断。本研究的结果确定了人Treg细胞抑制的新机制，其诱导靶向应答T细胞衰老，并为开发能够预防和/或逆转Treg诱导的免疫抑制的策略提供了新的见解。
Regulatory T (Treg) cells have broad suppressive activity on host immunity, but the fate and function of suppressed responder T cells remains largely unknown. In the present study, we report that human Treg cells can induce senescence in responder naive and effector T cells in vitro and in vivo. Senescent responder T cells induced by human Treg cells changed their phenotypes and cytokine profiles and had potent suppressive function. Furthermore, Treg-mediated molecular control of senescence in responder T cells was associated with selective modulation of p38 and ERK1/2 signaling and cell-cycle-regulatory molecules p16, p21, and p53. We further revealed that human Treg-induced senescence and suppressor function could be blocked by TLR8 signaling and/or by specific ERK1/2 and p38 inhibition in vitro and in vivo in animal models. The results of the present study identify a novel mechanism of human Treg cell suppression that induces targeted responder T-cell senescence and provide new insights relevant for the development of strategies capable of preventing and/or reversing Treg-induced immune suppression.