During an immune response to microbial infection, CD8+ T cells give rise to distinct classes of cellular progeny that coordinately mediate clearance of the pathogen and provide long-lasting protection against reinfection, including a subset of noncirculating tissue-resident memory (TRM) cells that mediate potent protection within nonlymphoid tissues. Here, we used single-cell RNA sequencing to examine the gene expression patterns of individual CD8+ T cells in the spleen and small intestine intraepithelial lymphocyte (siIEL) compartment throughout the course of their differentiation in response to viral infection. These analyses revealed previously unknown transcriptional heterogeneity within the siIEL CD8+ T cell population at several stages of differentiation, representing functionally distinct TRM cell subsets and a subset of TRM cell precursors within the tissue early in infection. Together, these findings may inform strategies to optimize CD8+ T cell responses to protect against microbial infection and cancer.

中文翻译：

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通过单细胞 RNA 测序揭示组织驻留记忆 CD8+ T 淋巴细胞的早期前体和分子决定因素。


在针对微生物感染的免疫反应过程中，CD8+ T 细胞会产生不同类别的细胞后代，协调介导病原体的清除并提供针对再次感染的持久保护，其中包括介导病原体的非循环组织驻留记忆 (TRM) 细胞的子集非淋巴组织内的有效保护。在这里，我们使用单细胞 RNA 测序来检查脾和小肠上皮内淋巴细胞 (siIEL) 区室中单个 CD8+ T 细胞在响应病毒感染而分化的整个过程中的基因表达模式。这些分析揭示了 siIEL CD8+ T 细胞群在多个分化阶段中先前未知的转录异质性，代表了感染早期组织内功能不同的 TRM 细胞亚群和 TRM 细胞前体亚群。总之，这些发现可能为优化 CD8+ T 细胞反应以预防微生物感染和癌症的策略提供信息。