Altered IL-7Rα expression with aging and the potential implications of IL-7 therapy on CD8+ T-cell immune responses

Abstract

We investigated the effects of aging on the IL-7-mediated CD8(+) T-cell survival pathway and of IL-7 therapy on T-cell immunity. Cells expressing IL-7 receptor (IL-7R) alpha(high) and alpha(low) were identified in a CD45RA(+) effector memory (EMCD45RA+, CD45RA(+)CCR7(-)) CD8(+) T-cell subset. Elderly subjects (65 years and older) had an increased frequency of EMCD45RA+, IL7R alpha(low) CD8(+) T cells, leading to decreased STAT5 phosphorylation and survival responses to IL-7 compared with young subjects (40 years and younger). These EMCD45RA+ IL-7R alpha(low) cells were largely antigen experienced (CD27(-)CD28(-)), replicatively senescent (CD57(+)), and perforin(high) CD8+ T cells that had decreased IL-7R alpha mRNA, independent of guanine and adenine binding protein alpha (GABP alpha) and growth factor independence-1 (GFI1) expression. In measuring T-cell receptor (TCR) repertoires of EMCD45RA+ CD8(+) T cells, the elderly had a limited repertoire in IL-7R alpha(high) and IL-7R alpha(low) cells, whereas the young had a diverse repertoire in IL-Mahigh but not in IL-7R alpha(low) cells. These findings suggest that aging affects IL7% expression by EMCD45RA+ CD8(+) T cells, leading to impaired signaling and survival responses to IL-7, and that IL-7 therapy may improve the survival of EMCD45RA+ CD8(+) T cells with a diverse TCR repertoire in the young but not in the elderly.