加州大学Lisa E. Wagar研究组报道了人类T细胞的深度剖析定义了血液和扁桃体的区隔克隆和表型轨迹。该项研究成果发表在2025年11月26日出版的《免疫学》上。

该研究组对来自10名捐赠者的自体造血和扁桃体的570万个T细胞进行了单细胞测序。该团队确定了与扁桃体受限表型相关的克隆扩增的不同模式。血液和扁桃体之间的克隆共享低于先前的估计，并随着年龄的增长而增加。相同的T细胞受体（TCR）序列显示有限的一致性在他们的表型跨室。

此外，位置决定了抗原特异性T细胞的频率、克隆优势和表型。使用免疫类器官，课题组发现抗原暴露驱动从初始或组织驻留记忆池中功能不同的T细胞克隆。最后，课题组证明慢性感染对血液和扁桃体驻留T细胞中TCR库多样性的影响不同。这些数据强调了考虑组织特异性背景的必要性，以便准确测量TCR库并监测干扰治疗后的T细胞反应。

据介绍，98%的T细胞存在于组织中，然而几乎所有的人类T细胞分析都是在外周血中进行的。

附：英文原文

Title: Deep profiling of human T cells defines compartmentalized clones and phenotypic trajectories across blood and tonsils

Author: Suhas Sureshchandra, James Henderson, Elizabeth Levendosky, Sankalan Bhattacharyya, Jenna M. Kastenschmidt, Andrew M. Sorn, Mahina Tabassum Mitul, Timothy B. Yates, Evien Cheng, Aviv Benchorin, Kyle Batucal, Allyssa Daugherty, Samuel J.H. Murphy, Chandrani Thakur, Douglas Trask, Gurpreet Ahuja, Qiu Zhong, Annie Moisan, Andreas Tiffeau-Mayer, Naresha Saligrama, Lisa E. Wagar

Issue&Volume: 2025-11-26

Abstract: 98% of T cells reside in tissues, yet nearly all human T cell analyses are performed on peripheral blood. We performed single-cell sequencing of 5.7 million T cells from autologous blood and tonsils of ten donors. We identified distinct patterns of clonal expansion associated with tonsil-restricted phenotypes. Clonal sharing between blood and tonsils was lower than previous estimates and increased with age. Identical T cell receptor (TCR) sequences exhibited limited concordance in their phenotypes across compartments. Furthermore, location dictated the frequencies, clonal dominance, and phenotypes of antigen-specific T cells. Using immune organoids, we showed that antigen exposure drives functionally distinct T cell clones from naive or tissue-resident memory pools. Finally, we demonstrate that chronic infections influence TCR repertoire diversity differently in blood and tonsil-resident T cells. These data highlight the necessity of accounting for tissue-specific contexts to accurately measure the TCR repertoire and monitor T cell responses following perturbing therapies.

DOI: 10.1016/j.immuni.2025.10.025

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00479-0