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

Autor:	Bohacova P; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA., Terekhova M; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA., Tsurinov P; JetBrains Research, Paphos 8021, Cyprus., Mullins R; Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA., Husarcikova K; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA., Shchukina I; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA., Antonova AU; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA., Echalar B; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA., Kossl J; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA., Saidu A; Department of Emergency Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Francis T; Centre for Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London SE1 1UL, UK., Mannie C; Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA., Arthur L; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA., Harridge SDR; Centre for Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London SE1 1UL, UK., Kreisel D; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA., Mudd PA; Department of Emergency Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USA; Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, St. Louis, MO 63110, USA., Taylor AM; Department of Medicine, Cardiovascular Division, University of Virginia, Charlottesville, VA 22903, USA., McNamara CA; Department of Medicine, Cardiovascular Division, University of Virginia, Charlottesville, VA 22903, USA; Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, VA 22903, USA., Cella M; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA., Puram SV; Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA; Rob Ebert and Greg Stubblefield Head and Neck Tumor Center at Siteman Cancer Center, St. Louis, MO 63110, USA., van den Broek T; Center for Translational Immunology, University Medical Centre Utrecht, Utrecht University, Utrecht 3584CX, the Netherlands., van Wijk F; Center for Translational Immunology, University Medical Centre Utrecht, Utrecht University, Utrecht 3584CX, the Netherlands., Eghtesady P; Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA., Artyomov MN; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: martyomov@wustl.edu.
Jazyk:	angličtina
Zdroj:	Immunity [Immunity] 2024 Oct 08; Vol. 57 (10), pp. 2362-2379.e10. Date of Electronic Publication: 2024 Sep 24.
DOI:	10.1016/j.immuni.2024.08.019
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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