Prompt Antiviral Action of Pulmonary CD8+T-RM Cells Is Mediated by Rapid IFN-gamma Induction and Its Downstream ISGs in the Lung

文献类型： 外文期刊

第一作者： Jiang, Lang

作者： Jiang, Lang;Zhang, Linxia;He, Qian;Xu, Jianqing;Zhang, Xiaoyan;Jiang, Lang;Zhang, Linxia;He, Qian;Xu, Jianqing;Zhang, Xiaoyan;Jiang, Lang;Liu, Lu;Zhang, Miaomiao;Zhang, Linxia;Zhu, Cuisong;He, Qian;Zhao, Chen;Xu, Jianqing;Zhang, Xiaoyan;Liu, Lu;Ye, Lilin;Li, Zejun

作者机构：

关键词： influenza; lung-resident memory CD8 T cells; IFN-gamma; interferon-induced genes; inflammatory cytokines

期刊名称：FRONTIERS IN IMMUNOLOGY （ 影响因子：8.786； 五年影响因子：8.876 ）

ISSN： 1664-3224

年卷期： 2022 年 13 卷

页码：

收录情况： SCI

摘要： Growing lines of evidence supported the importance of CD8+ lung tissue resident memory T (T-RM) cells in protection against respiratory viruses, exemplified by influenza A virus. However, the underlying in vivo mechanism remains largely undetermined. Here, we used mouse infection models to dissect in vivo cross-protective activity of lung CD8+ T-RM cells. By simultaneously interrogating transcriptional dynamics in lung CD8+ T-RM cells and surrounding tissues during the early course of infection, we demonstrated that lung CD8+ T-RM cells react to antigen re-exposure within hours, manifested by IFN-gamma upregulation, and a tissue-wide interferon-stimulated gene (ISG) program is subsequently elicited. Using antibody-mediated IFN-gamma neutralization and IFN-gamma receptor knockout mice, we could show that the induction of several important antiviral ISGs required IFN-gamma signaling, so did the suppression of key inflammatory cytokines. Interestingly, there were also examples of ISGs unaffected in the absence of IFN-gamma activity. Collectively, focusing on in situ characterization of lung CD8+ T-RM cells during very early stage of infection, a critical period of host antiviral defense that has been poorly investigated, our studies highlight that these cells, once triggered by antigen re-exposure, are programmed to produce IFN-gamma expeditiously to promote a lung-wide antiviral response for effective virus control.

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