Immunity · 2024
Multidimensional profiling of human T cells reveals high CD38 expression, marking recent thymic emigrants and age-related naive T cell remodeling.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Bohacova Pavla, Terekhova Marina, Tsurinov Petr, Mullins Riley, Husarcikova Kamila, Shchukina Irina, Antonova Alina Ulezko, Echalar Barbora, Kossl Jan, Saidu Adam, Francis Thomas, Mannie Chelsea, Arthur Laura, Harridge Stephen D R, Kreisel Daniel, Mudd Philip A, Taylor Angela M, McNamara Coleen A, Cella Marina, Puram Sidharth V, van den Broek Theo, van Wijk Femke, Eghtesady Pirooz, Artyomov Maxim N
Аннотация
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.