Second Department of Internal Medicine, University of Tübingen, Tübingen, Germany.
Cancer Solutions Program, Health Sciences North Research Institute, Sudbury, ON, Canada.
Front Immunol. 2019 Jan 29;10:111. doi: 10.3389/fimmu.2019.00111. eCollection 2019.
T cell "exhaustion" describes a state of late-stage differentiation usually associated with active prevention of functionality via ligation of negative signaling receptors on the cell surface, and which can be reversed by blocking these interactions. This contrasts with T cell "senescence," which has been defined as a state that is maintained by intrinsic internal cell signaling (caused by DNA damage or other stresses) and which can be reversed pharmacologically. Interventions to alleviate these two different categories of inhibitory pathways may be desirable in immunotherapy for cancer and possibly certain infectious diseases, but reciprocally inducing and maintaining these states, or some properties thereof, may be beneficial in organ transplantation and autoimmunity. Even under physiological non-pathological conditions, T cell exhaustion and senescence may play a role in the retention of T cell clones required for immunosurveillance, and prevent their loss via elimination at the Hayflick limit. This essay briefly reviews T cell exhaustion in contrast to replicative senescence, and circumstances under which their modulation may be beneficial.
T 细胞“耗竭”描述了晚期分化的状态，通常与通过细胞表面负信号受体的连接主动防止功能有关，并且可以通过阻断这些相互作用来逆转。这与 T 细胞“衰老”形成对比，衰老被定义为一种由内在细胞信号（由 DNA 损伤或其他应激引起）维持的状态，并且可以通过药理学逆转。减轻这两种不同类别的抑制途径的干预措施可能在癌症和某些传染病的免疫治疗中是可取的，但是相互诱导和维持这些状态或其某些特性可能对器官移植和自身免疫有益。即使在生理非病理条件下，T 细胞耗竭和衰老也可能在保留免疫监视所需的 T 细胞克隆中发挥作用，并通过在海夫利克极限处消除来防止其丢失。本文简要回顾了 T 细胞耗竭与复制性衰老的对比，以及调节它们可能有益的情况。
