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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
Immunity ( IF 25.5 ) 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, Theo van den Broek, Femke van Wijk, Pirooz Eghtesady, Maxim N. Artyomov

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 CD38hi 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 CXCR3hi 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.

中文翻译:


人 T 细胞的多维分析显示 CD38 高表达,标志着近期胸腺迁移和年龄相关的幼稚 T 细胞重塑



胸腺退化是人类免疫衰老的关键因素,导致胸腺输出量减少和循环中近期胸腺迁移 (RTE) 幼稚 T 细胞减少。目前,人类 RTE 及其相应的细胞表面标志物的精确定义尚不清楚。单细胞 RNA-seq/ATAC-seq 数据分析通过 SOX4、IKZF2 和 TOX 以及 CD38 蛋白的表达来区分 RTE,从而表面 CD38hi 表达普遍识别 CD8 + 和 CD4 + RTE。我们进一步确定了 158 个个体队列中 RTE 和成熟细胞的动力学,包括与年龄相关的转录重编程和细胞因子产生的变化。光谱细胞术分析揭示了幼稚 CD8+ 和 CD4+ T 细胞共有的两个衰老轴:(1) CD38++ 细胞 (RTE) 减少和 (2) CXCR3hi 细胞增加。识别 RTE 有助于直接评估胸腺健康状况。此外,解决初始 T 细胞重塑的动力学可以深入了解整个衰老过程中的疫苗接种和感染反应性。
更新日期:2024-09-24
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