哥伦比亚大学Donna L. Farber团队在研究中取得进展。他们开发出人类循环和组织驻留记忆T细胞跨位点的异步老化和周转。2025年7月29日出版的《免疫学》杂志发表了这项成果。

该课题组研究人员研究了人类淋巴器官、粘膜部位和血液中T细胞的年龄相关动态，研究了超过10年的生命，主题是回顾性放射性碳（¹⁴C）出生年代测定，以及细胞、转录组和表观遗传谱。外周部位的记忆T细胞表现出持续的更新，平均寿命为1-2年，而脾脏含有更长寿的T细胞。随着年龄的增长，T_EM细胞表达衰老标志物和GZMK转录特征，而TR_M细胞保持位点特异性的常驻表型而不表现出衰老特征。T_EM和T_RM细胞均表现出与年龄相关的DNA低甲基化，尽管T_RM细胞表现出更多的表观遗传调控基因。总之，他们的发现揭示了人类记忆T细胞在亚群和部位上的非同步衰老，以及TRM细胞在没有免疫衰老的情况下的持久性。

据悉，记忆T细胞作为循环效应记忆（T_EM）和组织常驻（T_RM）群体在组织中维持保护性免疫，尽管位点和亚群在记忆持久性中的作用尚不明确。

附：英文原文

Title: Asynchronous aging and turnover of human circulating and tissue-resident memory T cells across sites

Author: Nora Lam, J. Carlos Angel, Bruce A. Buchholz, YoonSeung Lee, Stuart P. Weisberg, Brea H. Brown, Julia Davis-Porada, Daniel P. Caron, Isaac J. Jensen, Peter A. Szabo, Basak B. Ural, Steven B. Wells, Masaru Kubota, Rei Matsumoto, Maigan Brusko, Todd M. Brusko, Chao Lu, Andrew J. Yates, Donna L. Farber

Issue&Volume: 2025-07-29

Abstract: Memory T cells are maintained in tissues as circulating effector-memory (TEM) and tissue-resident (TRM) populations for protective immunity, though the role of site and subset in memory persistence remains undefined. Here, we investigated age-associated dynamics of human T cells in lymphoid organs, mucosal sites, and blood over 10 decades of life using retrospective radiocarbon (14C) birth dating, along with cellular, transcriptome, and epigenetic profiling. Memory T cells across peripheral sites exhibited continuous turnover with mean lifespans of 1–2 years, while the spleen contained longer-lived T cells. Over age, TEM cells expressed senescent markers and a GZMK transcriptional signature, while TRM cells maintained site-specific resident phenotypes without exhibiting features of senescence. Both TEM and TRM cells showed age-associated DNA hypomethylation, though TRM cells exhibited more epigenetically regulated genes. Together, our findings reveal asynchronous aging of human memory T cells by subset and site, as well as persistence of TRM cells without immunosenescence.

DOI: 10.1016/j.immuni.2025.07.001

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00310-3