John B. Little Center for Radiation Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Science, Department of Systems Biology, Harvard Medical School, Boston, MA, United States.
Int Rev Cell Mol Biol. 2019;342:27-71. doi: 10.1016/bs.ircmb.2018.07.004. Epub 2018 Aug 29.
Cell death plays two major complementary roles in T cell biology: mediating the removal of cells that are targeted by T cells and the removal of T cells themselves. T cells serve as major actors in the adaptive immune response and function by selectively killing cells which are infected or dysfunctional. This feature is highly involved during homeostatic maintenance, and is relied upon and modulated in the context of cancer immunotherapy. The vital recognition and elimination of both autoreactive T cells and cells which are unable to recognize threats is a highly selective and regulated process. Moreover, detection of potential threats will result in the activation and expansion of T cells, which on resolution of the immune response will need to be eliminated. The culling of these T cells can be executed via a multitude of cell death pathways which are used in context-specific manners. Failure of these processes may result in an accumulation of misdirected or dysfunctional T cells, leading to complications such as autoimmunity or cancer. This review will focus on the role of cell death regulation in the maintenance of T cell homeostasis, as well as T cell-mediated elimination of infected or dysfunctional cells, and will summarize and discuss the current knowledge of the cellular mechanisms which are implicated in these processes.
细胞死亡在 T 细胞生物学中发挥着两个主要的互补作用:介导被 T 细胞靶向的细胞的清除和 T 细胞自身的清除。T 细胞作为适应性免疫反应的主要参与者,通过选择性地杀死感染或功能失调的细胞来发挥作用。这一特性在体内平衡维持中起着至关重要的作用,并在癌症免疫治疗的背景下得到依赖和调节。对自身反应性 T 细胞和无法识别威胁的细胞的重要识别和消除是一个高度选择性和调节性的过程。此外,对潜在威胁的检测将导致 T 细胞的激活和扩增,而在免疫反应得到解决后,这些 T 细胞需要被消除。这些 T 细胞的清除可以通过多种细胞死亡途径来实现,这些途径在特定的情况下被使用。这些过程的失败可能导致定向错误或功能失调的 T 细胞的积累,导致自身免疫或癌症等并发症。本综述将重点讨论细胞死亡调控在 T 细胞体内平衡维持中的作用,以及 T 细胞介导的感染或功能失调细胞的清除,并将总结和讨论这些过程中涉及的细胞机制的现有知识。