Abstract
CD7− T cells constitute a distinct subset within the CD4+ and CD8+ T cell populations; their developmental and functional relationship to the majority of CD7+ T cells, however, remained so far unresolved. We here elucidate that CD7− cells represent aging T cells in late memory cell development characterized by a high activation threshold, low effector capacities, and high sensitivity to activation-induced cell death (AICD). In this regard, CD7− T cells highly express killer cell lectin-like receptor G1 (KLRG-1), harbor telomeres of shorter lengths, a decreased telomerase expression per cell, and less amounts of T cell receptor rearrangement excision circles (TRECs) compared to CD7+ cells. CD7− T cells are generated in vitro from naive CD7+ T cells upon repetitive TCR/CD28 engagement, a process that is unidirectional and requires multiple cell divisions. Consequently, clonal expansions of CD7− T cells in vivo are less frequent than of CD7+ T cells, the former can be traced back to those of CD7+ T cells.
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