Abstract

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.

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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