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Heterogenous Populations of Tissue-Resident CD8+ T Cells Are Generated in Response to Infection and Malignancy.
Immunity ( IF 25.5 ) Pub Date : 2020-05-19 , DOI: 10.1016/j.immuni.2020.04.007
J Justin Milner 1 , Clara Toma 1 , Zhaoren He 2 , Nadia S Kurd 3 , Quynh P Nguyen 1 , Bryan McDonald 1 , Lauren Quezada 3 , Christella E Widjaja 3 , Deborah A Witherden 1 , John T Crowl 1 , Laura A Shaw 1 , Gene W Yeo 2 , John T Chang 3 , Kyla D Omilusik 1 , Ananda W Goldrath 1
Affiliation  

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 Blimp1hiId3lo tissue-resident effector cell population most prominent in the early phase of acute viral and bacterial infections and a molecularly distinct Blimp1loId3hi 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.

中文翻译:

组织驻留 CD8+ T 细胞的异质群是响应感染和恶性肿瘤而产生的。

组织驻留记忆 CD8+ T 细胞 (Trm) 通过对非淋巴组织的持续监视提供宿主保护。使用单细胞 RNA 测序 (scRNA-seq) 和基因报告小鼠,我们鉴定了肠道抗原特异性 CD8+ T 细胞的离散谱系,包括在急性病毒和细菌感染早期最突出的 Blimp1hiId3lo 组织驻留效应细胞群感染和分子上不同的 Blimp1loId3hi 组织驻留记忆群体随后在后来的感染时间点积累。这些 Trm 群体表现出不同的细胞因子产生、次级记忆潜力和转录程序,包括转录调节因子 Blimp1、T-bet、Id2 和 Id3 在支持和维持肠道 Trm 方面的不同作用。将我们的分析扩展到恶性组织,我们还鉴定了效应样和记忆样 CD8+ T 细胞群的离散群体,其具有组织驻留基因表达特征,分别具有最终耗尽和祖细胞耗尽的 T 细胞的特征。我们的研究结果提供了对 Trm 细胞的发育和功能异质性的深入了解,这对增强疫苗接种和免疫治疗方法具有重要意义。
更新日期:2020-05-19
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