Pan Yi-Gen, Bartolo Laurent, Xu Ruozhang, Patel Bijal, Zarnitsyna Veronika, Su Laura
Department of Medicine, Division of Rheumatology, Perelman School of Medicine, Institute for Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Corporal Michael J Crescenz VA Medical Center, Philadelphia, PA, 19104, USA.
bioRxiv. 2024 Mar 14:2024.03.11.584523. doi: 10.1101/2024.03.11.584523.
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 (T) 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 stimulation. Single-cell TCR sequencing detected expanded clonotypes within the T subset and identified a shared repertoire with memory and effector T cells. T cells expressing T-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 T 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.
导致持久免疫记忆的因素仍未完全明了。在我们通过肽-MHC四聚体对黄热病病毒（YFV）疫苗的CD4 T细胞反应进行的纵向分析中，我们意外地发现了在免疫后持续数月至数年的初始表型病毒特异性CD4 T细胞。这些标记阴性T细胞（T细胞）缺乏CD95、CXCR3、CD11a和CD49d表面蛋白表达，这使它们与先前发现的干细胞记忆T细胞区分开来。在功能上，它们在受到刺激时类似于真正的初始T细胞。单细胞TCR测序在T细胞亚群中检测到了扩增的克隆型，并确定了与记忆T细胞和效应T细胞共享的库。表达与T细胞相关TCR的T细胞在接种疫苗前很少见，这表明它们在接种疫苗后会扩增。在随后几年对YFV特异性反应的纵向跟踪显示，T细胞亚群具有卓越的稳定性，并且它们与总体人群的长寿相关。这些长寿的、经历过抗原刺激的T细胞的鉴定可能为基于T细胞的持久疫苗和工程化T细胞疗法的设计提供参考。
