人类 T 细胞的多维图谱显示 CD38 高表达，标志着新近胸腺移民和与年龄相关的幼稚 T 细胞重塑

IF 25.5 1区医学 Q1 IMMUNOLOGY

Immunity Pub Date : 2024-09-24 DOI:10.1016/j.immuni.2024.08.019

Pavla Bohacova, Marina Terekhova, Petr Tsurinov, Riley Mullins, Kamila Husarcikova, Irina Shchukina, Alina Ulezko Antonova, Barbora Echalar, Jan Kossl, Adam Saidu, Thomas Francis, Chelsea Mannie, Laura Arthur, Stephen D.R. Harridge, Daniel Kreisel, Philip A. Mudd, Angela M. Taylor, Coleen A. McNamara, Marina Cella, Sidharth V. Puram, Maxim N. Artyomov

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引用次数: 0

摘要

胸腺内陷是人类免疫衰老的一个关键因素，它导致胸腺输出减少，循环中的新近胸腺移出（RTE）幼稚T细胞减少。目前，人类 RTE 及其相应细胞表面标志物的精确定义尚不明确。单细胞RNA-seq/ATAC-seq数据分析通过SOX4、IKZF2、TOX和CD38蛋白的表达来区分RTE，其中表面CD38hi的表达可普遍识别CD8+和CD4+ RTE。我们进一步确定了 158 人队列中 RTE 和成熟细胞的动态变化，包括与年龄相关的转录重编程和细胞因子产生的变化。光谱细胞分析法显示了幼稚 CD8+ 和 CD4+ T 细胞共同的两个衰老轴：（1）CD38++ 细胞（RTE）的减少；（2）CXCR3hi 细胞的增加。识别 RTE 可直接评估胸腺健康状况。此外，解析幼稚T细胞重塑的动态变化可深入了解整个衰老过程中的疫苗接种和感染反应能力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Multidimensional profiling of human T cells reveals high CD38 expression, marking recent thymic emigrants and age-related naive T cell remodeling

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Multidimensional profiling of human T cells reveals high CD38 expression, marking recent thymic emigrants and age-related naive T cell remodeling

Thymic involution is a key factor in human immune aging, leading to reduced thymic output and a decline in recent thymic emigrant (RTE) naive T cells in circulation. Currently, the precise definition of human RTEs and their corresponding cell surface markers lacks clarity. Analysis of single-cell RNA-seq/ATAC-seq data distinguished RTEs by the expression of SOX4, IKZF2, and TOX and CD38 protein, whereby surface CD38^hi expression universally identified CD8⁺ and CD4⁺ RTEs. We further determined the dynamics of RTEs and mature cells in a cohort of 158 individuals, including age-associated transcriptional reprogramming and shifts in cytokine production. Spectral cytometry profiling revealed two axes of aging common to naive CD8⁺ and CD4⁺ T cells: (1) a decrease in CD38⁺⁺ cells (RTEs) and (2) an increase in CXCR3^hi cells. Identification of RTEs enables direct assessment of thymic health. Furthermore, resolving the dynamics of naive T cell remodeling yields insight into vaccination and infection responsiveness throughout aging.

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来源期刊

Immunity 医学-免疫学

CiteScore

49.40

自引率

2.20%

发文量

205

审稿时长

6 months

期刊介绍： Immunity is a publication that focuses on publishing significant advancements in research related to immunology. We encourage the submission of studies that offer groundbreaking immunological discoveries, whether at the molecular, cellular, or whole organism level. Topics of interest encompass a wide range, such as cancer, infectious diseases, neuroimmunology, autoimmune diseases, allergies, mucosal immunity, metabolic diseases, and homeostasis.