Diao Huitian, Pipkin Matthew
Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, USA.
F1000Res. 2019 Jul 31;8. doi: 10.12688/f1000research.18211.1. eCollection 2019.
The process by which naïve CD8 T cells become activated, accumulate, and terminally differentiate as well as develop into memory cytotoxic T lymphocytes (CTLs) is central to the development of potent and durable immunity to intracellular infections and tumors. In this review, we discuss recent studies that have elucidated ancestries of short-lived and memory CTLs during infection, others that have shed light on gene expression programs manifest in individual responding cells and chromatin remodeling events, remodeling factors, and conventional DNA-binding transcription factors that stabilize the differentiated states after activation of naïve CD8 T cells. Several models have been proposed to conceptualize how naïve cells become memory CD8 T cells. A parsimonious solution is that initial naïve cell activation induces metastable gene expression in nascent CTLs, which act as progenitor cells that stochastically diverge along pathways that are self-reinforcing and result in shorter- versus longer-lived CTL progeny. Deciphering how regulatory factors establish and reinforce these pathways in CD8 T cells could potentially guide their use in immunotherapeutic contexts.
初始CD8 T细胞被激活、积累并最终分化以及发育为记忆性细胞毒性T淋巴细胞（CTL）的过程，对于产生针对细胞内感染和肿瘤的强大而持久的免疫力至关重要。在本综述中，我们讨论了最近的研究，这些研究阐明了感染期间短命CTL和记忆CTL的谱系，其他研究揭示了个体反应细胞中表现出的基因表达程序以及染色质重塑事件、重塑因子和传统DNA结合转录因子，这些因子在初始CD8 T细胞激活后稳定分化状态。已经提出了几种模型来解释初始细胞如何成为记忆性CD8 T细胞。一种简洁的解决方案是，初始初始细胞激活在新生CTL中诱导亚稳态基因表达，新生CTL作为祖细胞，沿着自我强化的途径随机分化，导致寿命较短和较长的CTL后代。解读调节因子如何在CD8 T细胞中建立和强化这些途径，可能会指导它们在免疫治疗中的应用。
