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

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Pages (from-to)	2362-2379.e10
Number of pages	18
Journal	Immunity
Volume	57
Issue number	10
DOIs	https://doi.org/10.1016/j.immuni.2024.08.019
Publication status	Published - 8 Oct 2024

Keywords

PBMC
aging
human
naive T cells
recent thymic emigrants

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Bohacova, P., Terekhova, M., Tsurinov, P., Mullins, R., Husarcikova, K., Shchukina, I., Antonova, A. U., Echalar, B., Kossl, J., Saidu, A., Francis, T., Mannie, C., Arthur, L., Harridge, S. D. R., Kreisel, D., Mudd, P. A., Taylor, A. M., McNamara, C. A., Cella, M., ... Artyomov, M. N. (2024). Multidimensional profiling of human T cells reveals high CD38 expression, marking recent thymic emigrants and age-related naive T cell remodeling. Immunity, 57(10), 2362-2379.e10. https://doi.org/10.1016/j.immuni.2024.08.019

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

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",

author = "Pavla Bohacova and Marina Terekhova and Petr Tsurinov and Riley Mullins and Kamila Husarcikova and Irina Shchukina and Antonova, {Alina Ulezko} and Barbora Echalar and Jan Kossl and Adam Saidu and Thomas Francis and Chelsea Mannie and Laura Arthur and Harridge, {Stephen D R} and Daniel Kreisel and Mudd, {Philip A} and Taylor, {Angela M} and McNamara, {Coleen A} and Marina Cella and Puram, {Sidharth V} and {van den Broek}, Theo and {van Wijk}, Femke and Pirooz Eghtesady and Artyomov, {Maxim N}",

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month = oct,

day = "8",

doi = "10.1016/j.immuni.2024.08.019",

language = "English",

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Bohacova, P, Terekhova, M, Tsurinov, P, Mullins, R, Husarcikova, K, Shchukina, I, Antonova, AU, Echalar, B, Kossl, J, Saidu, A, Francis, T, Mannie, C, Arthur, L, Harridge, SDR, Kreisel, D, Mudd, PA, Taylor, AM, McNamara, CA, Cella, M, Puram, SV, van den Broek, T , van Wijk, F, Eghtesady, P & Artyomov, MN 2024, 'Multidimensional profiling of human T cells reveals high CD38 expression, marking recent thymic emigrants and age-related naive T cell remodeling', Immunity, vol. 57, no. 10, pp. 2362-2379.e10. https://doi.org/10.1016/j.immuni.2024.08.019

TY - JOUR

T1 - Multidimensional profiling of human T cells reveals high CD38 expression, marking recent thymic emigrants and age-related naive T cell remodeling

AU - Bohacova, Pavla

AU - Terekhova, Marina

AU - Tsurinov, Petr

AU - Mullins, Riley

AU - Husarcikova, Kamila

AU - Shchukina, Irina

AU - Antonova, Alina Ulezko

AU - Echalar, Barbora

AU - Kossl, Jan

AU - Saidu, Adam

AU - Francis, Thomas

AU - Mannie, Chelsea

AU - Arthur, Laura

AU - Harridge, Stephen D R

AU - Kreisel, Daniel

AU - Mudd, Philip A

AU - Taylor, Angela M

AU - McNamara, Coleen A

AU - Cella, Marina

AU - Puram, Sidharth V

AU - van den Broek, Theo

AU - van Wijk, Femke

AU - Eghtesady, Pirooz

AU - Artyomov, Maxim N

PY - 2024/10/8

Y1 - 2024/10/8

N2 - 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.

AB - 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.

KW - PBMC

KW - aging

KW - human

KW - naive T cells

KW - recent thymic emigrants

UR - http://www.scopus.com/inward/record.url?scp=85206017153&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2024.08.019

DO - 10.1016/j.immuni.2024.08.019

M3 - Article

C2 - 39321807

SN - 1074-7613

VL - 57

SP - 2362-2379.e10

JO - Immunity

JF - Immunity

IS - 10

ER -

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

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