Longitudinal analysis reveals age-related changes in the T cell receptor repertoire of human T cell subsets

A diverse T cell receptor (TCR) repertoire is essential for protection against a variety of pathogens and T cell repertoire size is believed to decline with age. However, the precise size of human TCR repertoire in total and subsets of T cells, and their changes with age are not fully characterized....

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Bibliographic Details
Published in:The Journal of clinical investigation 2022-09, Vol.132 (17), p.1-13
Main Authors: Sun, Xiaoping, Nguyen, Thomas, Achour, Achouak, Ko, Annette, Cifello, Jeffrey, Ling, Chen, Sharma, Jay, Hiroi, Toyoko, Zhang, Yongqing, Chia, Chee W, Wood Iii, William, Wu, Wells W, Zukley, Linda, Phue, Je-Nie, Becker, Kevin G, Shen, Rong-Fong, Ferrucci, Luigi, Weng, Nan-Ping
Format: Article
Language:English
Subjects:
Adults
Age
Aging
Biomedical research
Blood
CD4 antigen
CD8 antigen
Cell receptors
Cytokines
Cytotoxicity
Disease susceptibility
Health aspects
Immunologic memory
Immunological memory
Immunological research
Lymphocytes
Lymphocytes T
Memory cells
Pathogens
Physiological aspects
T cell receptors
T cells
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Summary:A diverse T cell receptor (TCR) repertoire is essential for protection against a variety of pathogens and T cell repertoire size is believed to decline with age. However, the precise size of human TCR repertoire in total and subsets of T cells, and their changes with age are not fully characterized. We conducted a longitudinal analysis of the human blood TCRα and TCRβ repertoire of CD4+ and CD8+ T cell subsets using a unique molecular identifier (UMI) based RNAseq method. Thorough analysis of 1.9 x 108 T cells yielded the lower estimate of TCR repertoire richness in an adult at 3.8 x 108. Alterations of TCR repertoire with age were observed in all four subsets of T cells. The greatest reduction was observed in naïve CD8+ T cells; the greatest clonal expansion was in memory CD8+ T cells, and the highest increased retention of TCR sequences was in memory CD8+ T cells. Our results demonstrated that age-related TCR repertoire attrition is subset specific and more profound for CD8+ than CD4+ T cells, suggesting aging has a more profound impact on the cytotoxic than on the helper T cell functions. This may explain the increased susceptibility of older adults to the novel infections.
ISSN:1558-8238
0021-9738
1558-8238
DOI:10.1172/JCI158122