CD7(-) T cells are late memory cells generated from CD7(+) T cells

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.