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感染和恶性肿瘤会引起组织驻留CD8+T细胞的异质性
作者:小柯机器人 发布时间:2020/5/20 23:42:27

美国加州大学圣迭戈分校Ananda W. Goldrath、Kyla D. Omilusik等研究人员合作发现,感染和恶性肿瘤会引起组织驻留CD8+T细胞的异质性。这一研究成果发表在2020年5月19日出版的《免疫》上。

通过使用单细胞RNA测序(scRNA-seq)和遗传报告基因小鼠,研究人员鉴定了肠道抗原特异性CD8+T细胞的不同谱系,包括在急性病毒和细菌感染早期阶段最突出的Blimp1hiId3lo组织驻留效应细胞群,以及Blimp1loId3hi组织驻留记忆群体,这些细胞在以后的感染时间点积累。
 
这些组织驻留记忆T细胞(Trm)群体展示出独特的细胞因子产生、次级记忆潜能以及转录程序,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。
 
将这些分析扩展到恶性组织,研究人员还发现了不同的效应样和记忆样CD8+T细胞群,它们具有组织驻留的基因表达特征,即分别具有终末耗尽和祖细胞耗尽T细胞的特征。这些发现提供了对Trm细胞发育和功能异质性的了解,这对增强疫苗接种和免疫治疗方法具有重要意义。

据悉,组织驻留记忆CD8+T细胞(Trm)通过对非淋巴组织的连续监视提供宿主保护。

附:英文原文

Title: Heterogenous Populations of Tissue-Resident CD8+ T Cells Are Generated in Response to Infection and Malignancy

Author: J. Justin Milner, Clara Toma, Zhaoren He, Nadia S. Kurd, Quynh P. Nguyen, Bryan McDonald, Lauren Quezada, Christella E. Widjaja, Deborah A. Witherden, John T. Crowl, Laura A. Shaw, Gene W. Yeo, John T. Chang, Kyla D. Omilusik, Ananda W. Goldrath

Issue&Volume: 2020/05/19

Abstract: Tissue-resident memory CD8+ T cells (Trm) provide host protection through continuous surveillance of non-lymphoidtissues. Using single-cell RNA-sequencing (scRNA-seq) and genetic reporter mice, weidentified discrete lineages of intestinal antigen-specific CD8+ T cells, including a Blimp1hiId3lo tissue-resident effector cell population most prominent in the early phase of acuteviral and bacterial infections and a molecularly distinct Blimp1loId3hi tissue-resident memory population that subsequently accumulated at later infectiontime points. These Trm populations exhibited distinct cytokine production, secondarymemory potential, and transcriptional programs including differential roles for transcriptionalregulators Blimp1, T-bet, Id2, and Id3 in supporting and maintaining intestinal Trm.Extending our analysis to malignant tissue, we also identified discrete populationsof effector-like and memory-like CD8+ T cell populations with tissue-resident gene-expression signatures that shared featuresof terminally exhausted and progenitor-exhausted T cells, respectively. Our findingsprovide insight into the development and functional heterogeneity of Trm cells, whichhas implications for enhancing vaccination and immunotherapy approaches.

DOI: 10.1016/j.immuni.2020.04.007

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30165-5

期刊信息

Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新if:21.522
官方网址:https://www.cell.com/immunity/home
投稿链接:https://www.editorialmanager.com/immunity/default.aspx