Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA.
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Immunity. 2020 May 19;52(5):808-824.e7. doi: 10.1016/j.immuni.2020.04.007.
Tissue-resident memory CD8 T cells (Trm) provide host protection through continuous surveillance of non-lymphoid tissues. Using single-cell RNA-sequencing (scRNA-seq) and genetic reporter mice, we identified discrete lineages of intestinal antigen-specific CD8 T cells, including a Blimp1Id3 tissue-resident effector cell population most prominent in the early phase of acute viral and bacterial infections and a molecularly distinct Blimp1Id3 tissue-resident memory population that subsequently accumulated at later infection time points. These Trm populations exhibited distinct cytokine production, secondary memory potential, and transcriptional programs including differential roles for transcriptional regulators Blimp1, T-bet, Id2, and Id3 in supporting and maintaining intestinal Trm. Extending our analysis to malignant tissue, we also identified discrete populations of effector-like and memory-like CD8 T cell populations with tissue-resident gene-expression signatures that shared features of terminally exhausted and progenitor-exhausted T cells, respectively. Our findings provide insight into the development and functional heterogeneity of Trm cells, which has implications for enhancing vaccination and immunotherapy approaches.
组织驻留记忆 CD8 T 细胞（Trm）通过对非淋巴组织的持续监测为宿主提供保护。使用单细胞 RNA 测序（scRNA-seq）和遗传报告小鼠，我们鉴定了肠道抗原特异性 CD8 T 细胞的离散谱系，包括 Blimp1Id3 组织驻留效应细胞群，在急性病毒和细菌感染的早期阶段最为突出，以及随后在后期感染时间点积累的分子上不同的 Blimp1Id3 组织驻留记忆群体。这些 Trm 群体表现出不同的细胞因子产生、次级记忆潜能和转录程序，包括转录调节因子 Blimp1、T-bet、Id2 和 Id3 在支持和维持肠道 Trm 中的不同作用。将我们的分析扩展到恶性组织，我们还鉴定了具有组织驻留基因表达特征的效应样和记忆样 CD8 T 细胞群体，它们分别具有终末耗竭和祖细胞耗竭 T 细胞的特征。我们的研究结果为 Trm 细胞的发育和功能异质性提供了深入了解，这对增强疫苗接种和免疫治疗方法具有重要意义。
