Longitudinal analysis reveals age-related changes in the T cell receptor repertoire of human T cell subsets |
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| Authors: | Xiaoping Sun Thomas Nguyen Achouak Achour Annette Ko Jeffrey Cifello Chen Ling Jay Sharma Toyoko Hiroi Yongqing Zhang Chee W. Chia William Wood III Wells W. Wu Linda Zukley Je-Nie Phue Kevin G. Becker Rong-Fong Shen Luigi Ferrucci Nan-ping Weng |
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| Affiliation: | 1.Laboratory of Molecular Biology and Immunology.;2.Gene expression and Genomics Unit, Laboratory of Genetics and Genomics, and;3.Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, Maryland, USA.;4.Facility for Biotechnology Resources, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.;5.Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, Maryland, USA. |
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| Abstract: | A diverse T cell receptor (TCR) repertoire is essential for protection against a variety of pathogens, and TCR repertoire size is believed to decline with age. However, the precise size of human TCR repertoires, in both total and subsets of T cells, as well as 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–based (UMI-based) RNA-seq method. Thorough analysis of 1.9 × 108 T cells yielded the lower estimate of TCR repertoire richness in an adult at 3.8 × 108. Alterations of the TCR repertoire with age were observed in all 4 subsets of T cells. The greatest reduction was observed in naive CD8+ T cells, while 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 that aging has a more profound effect on cytotoxic as opposed to helper T cell functions. This may explain the increased susceptibility of older adults to novel infections. |
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| Keywords: | Aging |
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