Differentiation marker-negative CD4+ T cells persist after yellow fever virus vaccination and contribute to durable memory.
Differentiation marker-negative CD4+ T cells persist after yellow fever virus vaccination and contribute to durable memory.
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分化标记阴性 CD4 T 细胞在黄热病病毒疫苗接种后持续存在，并有助于持久记忆。
DOI：
10.1101/2024.03.11.584523
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Su,Laura
中科院分区：
文献类型：
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作者：
Pan,Yi-Gen;Bartolo,Laurent;Xu,Ruozhang;Patel,Bijal;Zarnitsyna,Veronika;Su,Laura
持久免疫记忆的因素仍然不完全清楚。在我们通过肽-MHC四聚体对黄热病病毒（YFV）疫苗的CD 4 + T细胞应答的纵向分析中，我们意外地发现了幼稚表型病毒特异性CD 4 + T细胞，这些细胞在免疫后持续数月至数年。这些标记阴性T细胞（TMN）缺乏CD 95，CXCR 3，CD 11 a和CD 49 d表面蛋白表达，将它们与先前发现的干细胞记忆T细胞区分开来。在功能上，它们在体外刺激时类似于真正的幼稚T细胞。单细胞TCR测序检测TMN亚群内扩增的克隆型，并确定了记忆和效应T细胞的共享库。表达TMN相关TCR的T细胞在疫苗接种前是罕见的，表明它们在疫苗接种后扩增。随后几年对YFV特异性反应的纵向跟踪显示TMN亚群的上级稳定性及其与总体人群寿命的相关性。这些长寿命的、抗原经历的T细胞的鉴定可以为持久的基于T细胞的疫苗和工程化T细胞疗法的设计提供信息。
Factors that contribute to durable immunological memory remain incompletely understood. In our longitudinal analyses of CD4+ T cell responses to the yellow fever virus (YFV) vaccine by peptide-MHC tetramers, we unexpectedly found naïve phenotype virus-specific CD4+ T cells that persisted months to years after immunization. These Marker negative T cells (TMN) lacked CD95, CXCR3, CD11a, and CD49d surface protein expression, distinguishing them from previously discovered stem-cell memory T cells. Functionally, they resembled genuine naïve T cells upon in vitro stimulation. Single-cell TCR sequencing detected expanded clonotypes within the TMN subset and identified a shared repertoire with memory and effector T cells. T cells expressing TMN-associated TCRs were rare before vaccination, suggesting their expansion following vaccination. Longitudinal tracking of YFV-specific responses over the subsequent years revealed superior stability of the TMN subset and their association with the longevity of the overall population. The identification of these long-lived, antigen-experienced T cells may inform the design of durable T cell-based vaccines and engineered T cell therapies.