Adaptive immunity to intracellular pathogens and tumors is mediated by antigen‐experienced CD8 T cells. Individual naive CD8 T cells have the potential to differentiate into a diverse array of antigen‐experienced subsets that exhibit distinct effector functions, life spans, anatomic positioning, and potential for regenerating an entirely new immune response during iterative pathogenic exposures. The developmental process by which activated naive cells undergo diversification involves regulation of chromatin structure and transcription but is not entirely understood. This review examines how alterations in chromatin structure, transcription factor binding, extracellular signals, and single‐cell gene expression explain the differential development of distinct effector (T_EFF) and memory (T_MEM) CD8 T cell subsets. Special emphasis is placed on how Runx proteins function with additional transcription factors to pioneer changes in chromatin accessibility and drive transcriptional programs that establish the core attributes of cytotoxic T lymphocytes, subdivide circulating and non‐circulating T_MEM cell subsets, and govern terminal differentiation. The discussion integrates the roles of specific cytokine signals, transcriptional circuits and how regulation of individual nucleosomes and RNA polymerase II activity can contribute to the process of differentiation. A model that integrates many of these features is discussed to conceptualize how activated CD8 T cells arrive at their fates.

中文翻译：

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控制记忆 CD8 T 细胞发育的 Runx 蛋白和转录机制

对细胞内病原体和肿瘤的适应性免疫是由抗原经历过的 CD8 T 细胞介导的。单个幼稚 CD8 T 细胞有可能分化成一系列不同的抗原经历亚群，这些亚群表现出不同的效应子功能、寿命、解剖定位，并有可能在反复的病原体暴露期间再生全新的免疫反应。激活的幼稚细胞经历多样化的发育过程涉及染色质结构和转录的调节，但尚不完全清楚。这篇综述探讨了染色质结构、转录因子结合、细胞外信号和单细胞基因表达的改变如何解释不同效应子 (T EFF ₎和记忆 (T _{MEM)的差异发育}) CD8 T 细胞亚群。特别强调 Runx 蛋白如何与额外的转录因子一起发挥作用，以开创染色质可及性的变化并驱动转录程序，从而建立细胞毒性 T 淋巴细胞的核心属性，细分循环和非循环 T MEM 细胞亚群，并控制终末_分化。讨论整合了特定细胞因子信号的作用、转录回路以及单个核小体和 RNA 聚合酶 II 活性的调节如何促进分化过程。讨论了一个集成了许多这些功能的模型，以概念化激活的 CD8 T 细胞如何到达它们的命运。