Sex- and age-specific aspects of human peripheral T-cell dynamics

Mika, Justyna; Yoshida, Kengo; Kusunoki, Yoichiro; Candéias, Serge M.; Polanska, Joanna

doi:10.3389/fimmu.2023.1224304

Sex- and age-specific aspects of human peripheral T-cell dynamics

Journal Article · Fri Oct 13 00:00:00 EDT 2023 · Frontiers in Immunology

DOI:https://doi.org/10.3389/fimmu.2023.1224304· OSTI ID:2470356

^[1]; ^[2]; ^[2]; ^[3]; ^[1]

Silesian University of Technology, Gliwice (Poland)
Radiation Effects Research Foundation (RERF), Hiroshima (Japan)
Université Grenoble Alpes (France)

Background: The diversity of the antigenic T cell receptor (TCR) repertoire clonally expressed on T lymphocytes is a key element of the adaptive immune system protective functions. A decline in diversity in the older adults is associated with health deterioration. This diversity is generated by the rearrangement of TRB genes coding for TCR chains during lymphocyte differentiation in the thymus, but is essentially maintained by peripheral T lymphocytes proliferation for most of life. Deep sequencing of rearranged TRB genes from blood cells allows the monitoring of peripheral T cell repertoire dynamics. We analysed two aspects of rearranged TRB diversity, related to T lymphocyte proliferation and to the distribution of the T cell clone size, in a collection of repertoires obtained from 1 to 74 years-old donors. Results: Our results show that peripheral T lymphocytes expansion differs according to the recombination status of their TRB loci. Their proliferation rate changes with age, with different patterns in men and women. T cell clone size becomes more heterogeneous with time, and, in adults, is always more even in women. Importantly, a longitudinal analysis of TRB repertoires obtained at ten years intervals from individual men and women confirms the findings of this cross-sectional study. Conclusions: Peripheral T lymphocyte proliferation partially depends on their thymic developmental history. The rate of proliferation of T cells differing in their TRB rearrangement status is different in men and women before the age of 18 years old, but similar thereafter.

View Accepted Manuscript (DOE)

Research Organization:: Radiation Effects Research Foundation (RERF), Hiroshima (Japan)

Sponsoring Organization:: European Social Fund; LABEX PRIMES; Silesian University of Technology; USDOE

OSTI ID:: 2470356

Journal Information:: Frontiers in Immunology, Journal Name: Frontiers in Immunology Vol. 14; ISSN 1664-3224

Publisher:: Frontiers Research FoundationCopyright Statement

Country of Publication:: United States

Language:: English

References (44)

Immune aging and autoimmunity Goronzy, Jörg J.; Weyand, Cornelia M. Cellular and Molecular Life Sciences, Vol. 69, Issue 10 https://doi.org/10.1007/s00018-012-0970-0	journal	April 2012
Low-dose radiation accelerates aging of the T-cell receptor repertoire in CBA/Ca mice Candéias, Serge M.; Mika, Justyna; Finnon, Paul Cellular and Molecular Life Sciences, Vol. 74, Issue 23 https://doi.org/10.1007/s00018-017-2581-2	journal	June 2017
The measurement of diversity in different types of biological collections Pielou, E. C. Journal of Theoretical Biology, Vol. 13 https://doi.org/10.1016/0022-5193(66)90013-0	journal	December 1966
The Repertoires of Circulating Human CD8+ Central and Effector Memory T Cell Subsets Are Largely Distinct Baron, Véronique; Bouneaud, Cécile; Cumano, Ana Immunity, Vol. 18, Issue 2 https://doi.org/10.1016/S1074-7613(03)00020-7	journal	February 2003
Sex, the aging immune system, and chronic disease Gubbels Bupp, Melanie R. Cellular Immunology, Vol. 294, Issue 2 https://doi.org/10.1016/j.cellimm.2015.02.002	journal	April 2015
T cell subset-specific susceptibility to aging Czesnikiewicz-Guzik, Marta; Lee, Won-Woo; Cui, Dapeng Clinical Immunology, Vol. 127, Issue 1 https://doi.org/10.1016/j.clim.2007.12.002	journal	April 2008
Aging-related changes in human T-cell repertoire over 20 years delineated by deep sequencing of peripheral T-cell receptors Yoshida, Kengo; Cologne, John B.; Cordova, Kismet Experimental Gerontology, Vol. 96 https://doi.org/10.1016/j.exger.2017.05.015	journal	October 2017
Age-related changes in the TRB and IGH repertoires in healthy adult males and females Gong, Mingxing; Li, Xueying; Zheng, Anqi Immunology Letters, Vol. 240 https://doi.org/10.1016/j.imlet.2021.10.002	journal	December 2021
Maintenance of Peripheral Naive T Cells Is Sustained by Thymus Output in Mice but Not Humans den Braber, Ineke; Mugwagwa, Tendai; Vrisekoop, Nienke Immunity, Vol. 36, Issue 2 https://doi.org/10.1016/j.immuni.2012.02.006	journal	February 2012
Successful and Maladaptive T Cell Aging Goronzy, Jörg J.; Weyand, Cornelia M. Immunity, Vol. 46, Issue 3 https://doi.org/10.1016/j.immuni.2017.03.010	journal	March 2017
Epigenetic control of Tcrb gene rearrangement Spicuglia, Salvatore; Pekowska, Aleksandra; Zacarias-Cabeza, Joaquin Seminars in Immunology, Vol. 22, Issue 6 https://doi.org/10.1016/j.smim.2010.07.002	journal	December 2010
A generalized boxplot for skewed and heavy-tailed distributions Bruffaerts, Christopher; Verardi, Vincenzo; Vermandele, Catherine Statistics & Probability Letters, Vol. 95 https://doi.org/10.1016/j.spl.2014.08.016	journal	December 2014
T-cell antigen receptor genes and T-cell recognition Davis, Mark M.; Bjorkman, Pamela J. Nature, Vol. 334, Issue 6181 https://doi.org/10.1038/334395a0	journal	August 1988
Selecting and maintaining a diverse T-cell repertoire Goldrath, Ananda W.; Bevan, Michael J. Nature, Vol. 402, Issue 6759 https://doi.org/10.1038/46218	journal	November 1999
Sex differences in immune responses Klein, Sabra L.; Flanagan, Katie L. Nature Reviews Immunology, Vol. 16, Issue 10 https://doi.org/10.1038/nri.2016.90	journal	August 2016
The many important facets of T-cell repertoire diversity Nikolich-Žugich, Janko; Slifka, Mark K.; Messaoudi, Ilhem Nature Reviews Immunology, Vol. 4, Issue 2 https://doi.org/10.1038/nri1292	journal	February 2004
Both age and gender affect thymic output: more recent thymic migrants in females than males as they age Pido-Lopez, J.; Imami, N.; Aspinall, R. Clinical and Experimental Immunology, Vol. 125, Issue 3 https://doi.org/10.1046/j.1365-2249.2001.01640.x	journal	December 2001
Nonrandom attrition of the naive CD8 ⁺ T-cell pool with aging governed by T-cell receptor:pMHC interactions Rudd, Brian D.; Venturi, Vanessa; Li, Gang Proceedings of the National Academy of Sciences, Vol. 108, Issue 33 https://doi.org/10.1073/pnas.1107594108	journal	August 2011
Diversity and clonal selection in the human T-cell repertoire Qi, Q.; Liu, Y.; Cheng, Y. Proceedings of the National Academy of Sciences, Vol. 111, Issue 36 https://doi.org/10.1073/pnas.1409155111	journal	August 2014
Thymic involution and rising disease incidence with age Palmer, Sam; Albergante, Luca; Blackburn, Clare C. Proceedings of the National Academy of Sciences, Vol. 115, Issue 8 https://doi.org/10.1073/pnas.1714478115	journal	February 2018
Effects of sex and aging on the immune cell landscape as assessed by single-cell transcriptomic analysis Huang, Zhaohao; Chen, Binyao; Liu, Xiuxing Proceedings of the National Academy of Sciences, Vol. 118, Issue 33 https://doi.org/10.1073/pnas.2023216118	journal	August 2021
The Effect of Aging on Susceptibility to Infection Gardner, I. D. Clinical Infectious Diseases, Vol. 2, Issue 5 https://doi.org/10.1093/clinids/2.5.801	journal	September 1980
Productive T-cell receptor beta-chain gene rearrangement: coincident regulation of cell cycle and clonality during development in vivo. Hoffman, E. S.; Passoni, L.; Crompton, T. Genes & Development, Vol. 10, Issue 8 https://doi.org/10.1101/gad.10.8.948	journal	April 1996
T‐Cell Phenotypes Predictive of Frailty and Mortality in Elderly Nursing Home Residents Johnstone, Jennie; Parsons, Robin; Botelho, Fernando Journal of the American Geriatrics Society, Vol. 65, Issue 1 https://doi.org/10.1111/jgs.14507	journal	October 2016
A Direct Estimate of the Human T Cell Receptor Diversity Arstila, T. P. Science, Vol. 286, Issue 5441 https://doi.org/10.1126/science.286.5441.958	journal	October 1999
Human thymopoiesis is influenced by a common genetic variant within the TCRA-TCRD locus Clave, Emmanuel; Araujo, Itauá Leston; Alanio, Cécile Science Translational Medicine, Vol. 10, Issue 457 https://doi.org/10.1126/scitranslmed.aao2966	journal	September 2018
IL-7 sustains CD31 expression in human naive CD4+ T cells and preferentially expands the CD31+ subset in a PI3K-dependent manner Azevedo, Rita I.; Soares, Maria Vieira D.; Barata, João T. Blood, Vol. 113, Issue 13 https://doi.org/10.1182/blood-2008-07-166223	journal	March 2009
Quantifying the development of the peripheral naive CD4+ T-cell pool in humans Bains, Iren; Antia, Rustom; Callard, Robin Blood, Vol. 113, Issue 22 https://doi.org/10.1182/blood-2008-10-184184	journal	May 2009
Slower immune system aging in women versus men in the Japanese population Hirokawa, Katsuiku; Utsuyama, Masanori; Hayashi, Yoshio Immunity & Ageing, Vol. 10, Issue 1 https://doi.org/10.1186/1742-4933-10-19	journal	May 2013
The effect of ageing on human lymphocyte subsets: comparison of males and females Yan, Jun; Greer, Judith M.; Hull, Renee Immunity & Ageing, Vol. 7, Issue 1 https://doi.org/10.1186/1742-4933-7-4	journal	March 2010
Age related human T cell subset evolution and senescence Li, Mingde; Yao, Danlin; Zeng, Xiangbo Immunity & Ageing, Vol. 16, Issue 1 https://doi.org/10.1186/s12979-019-0165-8	journal	September 2019
In-depth immune cellular profiling reveals sex-specific associations with frailty Samson, Leonard Daniël; Boots, A. Mieke H.; Ferreira, José A. Immunity & Ageing, Vol. 17, Issue 1 https://doi.org/10.1186/s12979-020-00191-z	journal	June 2020
Immunosenescence: a key player in cancer development Lian, Jingyao; Yue, Ying; Yu, Weina Journal of Hematology & Oncology, Vol. 13, Issue 1 https://doi.org/10.1186/s13045-020-00986-z	journal	November 2020
Annotation of pseudogenic gene segments by massively parallel sequencing of rearranged lymphocyte receptor loci Dean, Jared; Emerson, Ryan O.; Vignali, Marissa Genome Medicine, Vol. 7, Issue 1 https://doi.org/10.1186/s13073-015-0238-z	journal	November 2015
TCRβ repertoire of CD4+ and CD8+ T cells is distinct in richness, distribution, and CDR3 amino acid composition Li, Hoi Ming; Hiroi, Toyoko; Zhang, Yongqing Journal of Leukocyte Biology, Vol. 99, Issue 3 https://doi.org/10.1189/jlb.6A0215-071RR	journal	September 2015
Cell generation dynamics underlying naive T-cell homeostasis in adult humans Mold, Jeff E.; Réu, Pedro; Olin, Axel PLOS Biology, Vol. 17, Issue 10 https://doi.org/10.1371/journal.pbio.3000383	journal	October 2019
Fitting Linear Mixed-Effects Models Using lme4 Bates, Douglas; Mächler, Martin; Bolker, Ben Journal of Statistical Software, Vol. 67, Issue 1 https://doi.org/10.18637/jss.v067.i01	journal	January 2015
The Effects of Androgens on T Cells: Clues to Female Predominance in Autoimmune Liver Diseases? Henze, Lara; Schwinge, Dorothee; Schramm, Christoph Frontiers in Immunology, Vol. 11 https://doi.org/10.3389/fimmu.2020.01567	journal	July 2020
Quantifying Thymic Export: Combining Models of Naive T Cell Proliferation and TCR Excision Circle Dynamics Gives an Explicit Measure of Thymic Output Bains, Iren; Thiébaut, Rodolphe; Yates, Andrew J. The Journal of Immunology, Vol. 183, Issue 7 https://doi.org/10.4049/jimmunol.0900743	journal	September 2009
Age-Related Decrease in TCR Repertoire Diversity Measured with Deep and Normalized Sequence Profiling Britanova, Olga V.; Putintseva, Ekaterina V.; Shugay, Mikhail The Journal of Immunology, Vol. 192, Issue 6 https://doi.org/10.4049/jimmunol.1302064	journal	February 2014
Dynamics of Individual T Cell Repertoires: From Cord Blood to Centenarians Britanova, Olga V.; Shugay, Mikhail; Merzlyak, Ekaterina M. The Journal of Immunology, Vol. 196, Issue 12 https://doi.org/10.4049/jimmunol.1600005	journal	June 2016
The Influence of Age on T Cell Generation and TCR Diversity Naylor, Keith; Li, Guangjin; Vallejo, Abbe N. The Journal of Immunology, Vol. 174, Issue 11 https://doi.org/10.4049/jimmunol.174.11.7446	journal	May 2005
Activation of Thymic Regeneration in Mice and Humans following Androgen Blockade Sutherland, Jayne S.; Goldberg, Gabrielle L.; Hammett, Maree V. The Journal of Immunology, Vol. 175, Issue 4 https://doi.org/10.4049/jimmunol.175.4.2741	journal	August 2005
The naive T-cell receptor repertoire has an extremely broad distribution of clone sizes de Greef, Peter C.; Oakes, Theres; Gerritsen, Bram eLife, Vol. 9 https://doi.org/10.7554/eLife.49900	journal	March 2020

Similar Records

Clonal heterogeneity of synovial fluid T lymphocytes from patients with rheumatoid arthritis

Journal Article · Tue Aug 01 00:00:00 EDT 1989 · Proceedings of the National Academy of Sciences of the United States of America; (USA) · OSTI ID:7168223

Arrested rearrangement of TCR V[beta] genes in thymocytes from children with x-linked severe combined immunodeficiency disease

Journal Article · Fri Jul 01 00:00:00 EDT 1994 · Journal of Immunology; (United States) · OSTI ID:6701233

Influence of age on the proliferation and peripheralization of thymic T cells

Journal Article · Thu Dec 31 23:00:00 EST 1987 · Arch. Pathol.; (United States) · OSTI ID:5407235

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
TCR
aging
homeostasis
immunology
modelling
repertoire diversity

Sex- and age-specific aspects of human peripheral T-cell dynamics

Citation Formats

References (44)

Similar Records

Related Subjects