Stability and flexibility in chromatin structure and transcription underlies memory CD8 T-cell differentiation.
Stability and flexibility in chromatin structure and transcription underlies memory CD8 T-cell differentiation.
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DOI：
10.12688/f1000research.18211.1
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发表时间：
2019-01-01
期刊：
影响因子：
--
通讯作者：
Pipkin, Matthew
中科院分区：
文献类型：
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作者：
Diao, Huitian;Pipkin, Matthew
初始CD8 T细胞被激活、积累、最终分化并发展为记忆细胞毒性T淋巴细胞（ctl）的过程是对细胞内感染和肿瘤产生有效和持久免疫的关键。在这篇综述中，我们讨论了最近的一些研究，这些研究阐明了感染期间短期和记忆型ctl的起源，其他研究揭示了在个体应答细胞和染色质重塑事件中表现的基因表达程序，重塑因子，以及在初始CD8 T细胞激活后稳定分化状态的传统dna结合转录因子。已经提出了几个模型来概念化幼稚细胞如何成为记忆性CD8 T细胞。一个简单的解决方案是，初始初始细胞激活诱导新生CTL的亚稳态基因表达，这些细胞作为祖细胞，随机地沿着自我强化的途径分化，导致CTL后代的寿命较短或较长。破译调节因子如何在CD8 T细胞中建立和加强这些途径，可能会指导它们在免疫治疗背景下的应用。
The process by which naive 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 naive CD8 T cells. Several models have been proposed to conceptualize how naive cells become memory CD8 T cells. A parsimonious solution is that initial naive 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.