Airway surveillance and lung viral control by memory T cells induced by COVID-19 mRNA vaccine.
Airway surveillance and lung viral control by memory T cells induced by COVID-19 mRNA vaccine.
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新冠肺炎基因疫苗诱导的记忆T细胞对呼吸道监测和肺病毒控制的研究
DOI：
10.1172/jci.insight.172510
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发表时间：
2023-11-22
期刊：
影响因子：
8
通讯作者：
Suresh, M.
中科院分区：
文献类型：
--
作者：
Kingstad-Bakke, Brock;Cleven, Thomas;Bussan, Hailey;Yount Jr., Boyd L.;Uraki, Ryuta;Iwatsuki-Horimoto, Kiyoko;Koga, Michiko;Yamamoto, Shinya;Yotsuyanagi, Hiroshi;Park, Hongtae;Mishra, Jay S.;Kumar, Sathish;Baric, Ralph S.;Halfmann, Peter J.;Kawaoka, Yoshihiro;Suresh, M.
尽管SARS-CoV-2的进化带来了一系列持续的抗体逃避病毒变体，但COVID-19 mRNA疫苗提供了强大的保护，可以抵御严重疾病和住院治疗。在这里，我们询问mRNA疫苗诱导的记忆T细胞是否限制肺SARS-CoV-2复制和严重疾病。我们发现，接受加强BioNTech mRNA疫苗的小鼠和人产生了有效的CD 8 T细胞应答，并显示出表达颗粒酶B/穿孔素的效应CD 8 T细胞的扩增和收缩动力学相似。单价和二价mRNA疫苗均引起脾、腹股沟和纵隔淋巴结、肺血管系统中以及最令人惊讶地在气道中的末端效应物和记忆前体效应物CD 8 T细胞的异质库的强烈扩增，这提示了全身和区域监测。此外，我们记录：（a）CD 8 T细胞记忆在多个组织中持续> 200天;（B）在用致病性SARS-CoV-2攻击后，循环记忆CD 8 T细胞通过需要CD 4 T细胞帮助的机制迅速外渗到肺并促进快速的病毒清除;和（c）过继转移的脾记忆CD 8 T细胞运输到气道并促进肺SARS-CoV-2清除。这些发现提供了对记忆T细胞在预防抗体逃避型SARS-CoV-2变异体突破性感染后严重肺部疾病中的关键作用的见解。
Although SARS-CoV-2 evolution seeds a continuous stream of antibody-evasive viral variants, COVID-19 mRNA vaccines provide robust protection against severe disease and hospitalization. Here, we asked whether mRNA vaccine–induced memory T cells limit lung SARS-CoV-2 replication and severe disease. We show that mice and humans receiving booster BioNTech mRNA vaccine developed potent CD8 T cell responses and showed similar kinetics of expansion and contraction of granzyme B/perforin-expressing effector CD8 T cells. Both monovalent and bivalent mRNA vaccines elicited strong expansion of a heterogeneous pool of terminal effectors and memory precursor effector CD8 T cells in spleen, inguinal and mediastinal lymph nodes, pulmonary vasculature, and most surprisingly in the airways, suggestive of systemic and regional surveillance. Furthermore, we document that: (a) CD8 T cell memory persists in multiple tissues for > 200 days; (b) following challenge with pathogenic SARS-CoV-2, circulating memory CD8 T cells rapidly extravasate to the lungs and promote expeditious viral clearance, by mechanisms that require CD4 T cell help; and (c) adoptively transferred splenic memory CD8 T cells traffic to the airways and promote lung SARS-CoV-2 clearance. These findings provide insights into the critical role of memory T cells in preventing severe lung disease following breakthrough infections with antibody-evasive SARS-CoV-2 variants.
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DOI：
10.1084/jem.20220780
发表时间：
2022-10-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
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影响因子：
7.3
作者：
通讯作者：
--
影响因子：
11.1
作者：
Chen, Yanxia;Song, Wenchen;Li, Can;Wang, Jiaxuan;Liu, Feifei;Ye, Zhanhong;Ren, Peidi;Tong, Yihan;Li, Junhua;Ou, Zhihua;Lee, Andrew Chak-Yiu;Cai, Jian-Piao;Wong, Bosco Ho-Yin;Chan, Jasper Fuk-Woo;Yuen, Kwok-Yung;Zhang, AnnaJin-Xia;Chu, Hin
通讯作者：
Chu, Hin
影响因子：
32.4
作者：
Gerlach, Carmen;Moseman, E. Ashley;Loughhead, Scott M.;Alvarez, David;Zwijnenburg, Anthonie J.;Waanders, Lisette;Garg, Rohit;de la Torre, Juan C.;von Andrian, Ulrich H.
通讯作者：
von Andrian, Ulrich H.
影响因子：
6.7
作者：
Gasper DJ;Neldner B;Plisch EH;Rustom H;Carrow E;Imai H;Kawaoka Y;Suresh M
通讯作者：
Suresh M