Memory T cells continuously accumulate with various degrees of selective clonal expansion after new or repeated immune responses ( 7, 8). Production of naive T cells substantially declines after puberty, creating a challenge to maintaining a T cell system throughout a lifetime that balances the numbers of naive and memory T cells ( 5, 6). Naive T cells produced by the thymus have the potential to recognize any pathogen, whereas memory T cells are generated from a past immunological response and offer long-lasting protection against pathogens during a subsequent encounter ( 1– 4). This may explain the increased susceptibility of older adults to novel infections. 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. 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. Alterations of the TCR repertoire with age were observed in all 4 subsets of T cells. Thorough analysis of 1.9 × 10 8 T cells yielded the lower estimate of TCR repertoire richness in an adult at 3.8 × 10 8. 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. 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. 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.
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