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Maintenance and functional regulation of immune memory to COVID-19 vaccines in tissues
Immunity ( IF 25.5 ) Pub Date : 2024-11-06 , DOI: 10.1016/j.immuni.2024.10.003
Julia Davis-Porada, Alex B. George, Nora Lam, Daniel P. Caron, Joshua I. Gray, Jenny Huang, Jennifer Hwu, Steven B. Wells, Rei Matsumoto, Masaru Kubota, YoonSeung Lee, Rory Morrison-Colvin, Isaac J. Jensen, Basak B. Ural, Namir Shaabani, Daniela Weiskopf, Alba Grifoni, Alessandro Sette, Peter A. Szabo, John R. Teijaro, Donna L. Farber

Memory T and B cells in tissues are essential for protective immunity. Here, we performed a comprehensive analysis of the tissue distribution, phenotype, durability, and transcriptional profile of COVID-19 mRNA vaccine-induced immune memory across blood, lymphoid organs, and lungs obtained from 63 vaccinated organ donors aged 23–86, some of whom experienced SARS-CoV-2 infection. Spike (S)-reactive memory T cells were detected in lymphoid organs and lungs and variably expressed tissue-resident markers based on infection history, and S-reactive B cells comprised class-switched memory cells resident in lymphoid organs. Compared with blood, S-reactive tissue memory T cells persisted for longer times post-vaccination and were more prevalent with age. S-reactive T cells displayed site-specific subset compositions and functions: regulatory cell profiles were enriched in tissues, while effector and cytolytic profiles were more abundant in circulation. Our findings reveal functional compartmentalization of vaccine-induced T cell memory where surveilling effectors and in situ regulatory responses confer protection with minimal tissue damage.

中文翻译:


组织中对 COVID-19 疫苗免疫记忆的维持和功能调节



组织中的记忆 T 细胞和 B 细胞对于保护性免疫至关重要。在这里,我们对 63 名 23-86 岁接种疫苗的器官供体获得的 COVID-19 mRNA 疫苗诱导的免疫记忆在血液、淋巴器官和肺部的组织分布、表型、持久性和转录谱进行了全面分析,其中一些人经历了 SARS-CoV-2 感染。在淋巴器官和肺中检测到刺突 (S) 反应性记忆 T 细胞,并根据感染史可变表达组织驻留标志物,S 反应性 B 细胞由驻留在淋巴器官中的类别转换记忆细胞组成。与血液相比,S 反应性组织记忆 T 细胞在接种疫苗后持续的时间更长,并且随着年龄的增长而更普遍。S 反应性 T 细胞显示出位点特异性亚群组成和功能:调节细胞谱在组织中富集,而效应细胞谱和溶细胞谱在循环中更丰富。我们的研究结果揭示了疫苗诱导的 T 细胞记忆的功能区室化,其中监视效应子和原位调节反应以最小的组织损伤提供保护。
更新日期:2024-11-06
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