Search

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 TCR[alpha] and TCR[beta] repertoire of [CD4.sup.+] and [CD8.sup.+] T cell subsets using a unique molecular identifier-based (UMI-based) RNA-seq method. Thorough analysis of 1.9 x [10.sup.8] T cells yielded the lower estimate of TCR repertoire richness in an adult at 3.8 x [10.sup.8]. Alterations of the TCR repertoire with age were observed in all 4 subsets of T cells. The greatest reduction was observed in naive [CD8.sup.+] T cells, while the greatest clonal expansion was in memory [CD8.sup.+] T cells, and the highest increased retention of TCR sequences was in memory [CD8.sup.+] T cells. Our results demonstrated that age-related TCR repertoire attrition is subset specific and more profound for [CD8.sup.+] than [CD4.sup.+] 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., Introduction 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 [...]