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 Puram; Theo van den Broek; Femke van Wijk; Pirooz Eghtesady; Maxim N Artyomov

doi:10.1016/j.immuni.2024.08.019

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

Immunity. 2024 Oct 8;57(10):2362-2379.e10. doi: 10.1016/j.immuni.2024.08.019. Epub 2024 Sep 24.

Authors

Pavla Bohacova¹, Marina Terekhova¹, Petr Tsurinov², Riley Mullins³, Kamila Husarcikova¹, Irina Shchukina¹, Alina Ulezko Antonova¹, Barbora Echalar¹, Jan Kossl¹, Adam Saidu⁴, Thomas Francis⁵, Chelsea Mannie⁶, Laura Arthur¹, Stephen D R Harridge⁵, Daniel Kreisel⁷, Philip A Mudd⁸, Angela M Taylor⁹, Coleen A McNamara¹⁰, Marina Cella¹, Sidharth V Puram¹¹, Theo van den Broek¹², Femke van Wijk¹², Pirooz Eghtesady⁶, Maxim N Artyomov¹³

Affiliations

¹ Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
² JetBrains Research, Paphos 8021, Cyprus.
³ 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.
⁴ Department of Emergency Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
⁵ 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.
⁶ Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
⁷ 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.
⁸ 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.
⁹ Department of Medicine, Cardiovascular Division, University of Virginia, Charlottesville, VA 22903, USA.
¹⁰ 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.
¹¹ 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.
¹² Center for Translational Immunology, University Medical Centre Utrecht, Utrecht University, Utrecht 3584CX, the Netherlands.
¹³ Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: [email protected].

PMID: 39321807
DOI: 10.1016/j.immuni.2024.08.019

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 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.

Keywords: PBMC; aging; human; naive T cells; recent thymic emigrants.

MeSH terms

ADP-ribosyl Cyclase 1* / metabolism
Adult
Aged
Aged, 80 and over
Aging* / immunology
CD4-Positive T-Lymphocytes / immunology
CD4-Positive T-Lymphocytes / metabolism
CD8-Positive T-Lymphocytes* / immunology
Female
Gene Expression Profiling
Humans
Male
Membrane Glycoproteins / genetics
Membrane Glycoproteins / metabolism
Middle Aged
Receptors, CXCR3 / metabolism
Single-Cell Analysis
Thymus Gland* / immunology
Thymus Gland* / metabolism
Young Adult

Substances

ADP-ribosyl Cyclase 1
Receptors, CXCR3
CD38 protein, human
Membrane Glycoproteins
CXCR3 protein, human