Dynamic changes in chromatin accessibility in CD8+ T cells responding to viral infection

In response to acute infection, naive CD8+ T cells expand, differentiate into effector cells and then contract to a long-lived pool of memory cells after pathogen clearance. During chronic infections or in tumors, CD8+ T cells acquire an “exhausted” phenotype. Here we present genome-wide comparisons of chromatin accessibility and gene expression from endogenous CD8+ T cells responding to acute and chronic viral infection using ATAC-seq and RNA-seq. Acquisition of effector, memory or exhausted phenotypes was associated with stable changes in chromatin accessibility away from the naive T cell state. Regions differentially accessible between functional subsets in vivo were enriched for binding sites of transcription factors known to regulate these subsets, including E2A, BATF, IRF4, T-bet and TCF1. Exhaustion-specific accessible regions were enriched for consensus binding sites for NFAT and Nr4a family members, indicating that chronic stimulation confers a unique accessibility profile on exhausted cells. Chromatin accessibility with ATAC-seq and gene expression with RNA-seq for CD8 T cell subsets after in vivo response to viral infection or after in vitro culture (total 44 samples)

针对急性感染，初始CD8+ T细胞会发生扩增并分化为效应细胞，随后在病原体被清除后收缩为长寿记忆细胞池。在慢性感染或肿瘤环境中，CD8+ T细胞会获得「耗竭」表型。本研究通过ATAC-seq与RNA-seq技术，对响应急性与慢性病毒感染的内源性CD8+ T细胞的染色质可及性与基因表达开展全基因组水平比较分析。效应、记忆或耗竭表型的获得，均伴随与初始T细胞状态相背离的染色质可及性稳定改变。体内功能亚群间差异可及的染色质区域，富集有已知调控这些亚群的转录因子结合位点，包括E2A、BATF、IRF4、T-bet与TCF1。耗竭特异性可及区域富集有NFAT与Nr4a家族成员的共识结合位点，表明慢性刺激会赋予耗竭细胞独特的染色质可及性图谱。本数据集包含经ATAC-seq检测的染色质可及性数据与经RNA-seq检测的基因表达数据，样本来自体内响应病毒感染或体外培养的CD8 T细胞亚群，共计44个样本。