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

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. PuramTheo van den Broek, Femke van Wijk, Pirooz Eghtesady, Maxim N. Artyomov

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2362-2379.e10
JournalImmunity
Volume57
Issue number10
DOIs
StatePublished - Oct 8 2024

Keywords

  • PBMC
  • aging
  • human
  • naive T cells
  • recent thymic emigrants

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