After resolution of infection, T cells differentiate into long-lived memory cells that recirculate through secondary lymphoid organs or establish residence in tissues. In contrast to CD8 + tissue-resident memory T cells (T RM ), the developmental origins and transcriptional regulation of CD4 + T RM remain largely undefined. Here, we investigated the phenotypic, functional, and transcriptional profiles of CD4 + T RM in the small intestine (SI) responding to acute viral infection, revealing a shared gene expression program and chromatin accessibility profile with circulating T H 1 and the progressive acquisition of a mature T RM program. Single-cell RNA sequencing identified heterogeneity among established CD4 + T RM , which were predominantly located in the lamina propria, and revealed a population of cells that coexpressed both effector- and memory-associated genes, including the transcriptional regulators Blimp1, Id2, and Bcl6. T H 1-associated Blimp1 and Id2 and T FH -associated Bcl6 were required for early T RM formation and development of a mature T RM population in the SI. These results demonstrate a developmental relationship between T H 1 effector cells and the establishment of early T RM , as well as highlighted differences in CD4 + versus CD8 + T RM populations, providing insights into the mechanisms underlying the origins, differentiation, and persistence of CD4 + T RM in response to viral infection.

中文翻译：

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病毒感染中 CD4 + T RM 分化的转录编程平衡效应和记忆相关基因表达


感染消退后，T 细胞分化为长寿命记忆细胞，通过次级淋巴器官再循环或在组织中定居。与CD8相比+组织驻留记忆 T 细胞（T RM ）、CD4的发育起源和转录调控+时间RM很大程度上仍然是未定义的。在这里，我们研究了 CD4 的表型、功能和转录谱+时间RM在小肠 (SI) 中对急性病毒感染做出反应，揭示了与循环 T 共享的基因表达程序和染色质可及性特征H 1、逐步获得成熟的T RM程序。单细胞 RNA 测序鉴定了已建立的 CD4 之间的异质性+时间RM ，它们主要位于固有层，并揭示了一群共表达效应器相关基因和记忆相关基因的细胞，包括转录调节因子 Blimp1、Id2 和 Bcl6。时间H 1 关联的 Blimp1 和 Id2 和 T跳频-早期T需要相关的Bcl6 RM成熟T的形成和发展RM SI 中的人口。 这些结果证明了 T 之间的发育关系H 1 效应细胞与早期T的建立RM ，以及 CD4 中突出显示的差异+与 CD8 +时间RM人群，深入了解 CD4 的起源、分化和持久性的机制+时间RM以应对病毒感染。