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

Abstract

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) αhigh and αlow 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+ IL-7Rαlow 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-7Rαlow cells were largely antigen experienced (CD27-CD28-), replicatively senescent (CD57+), and perforinhigh CD8+ T cells that had decreased IL-7Rα mRNA, independent of guanine and adenine binding protein α (GABPα) 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-7Rαhigh and IL-7Rαlow cells, whereas the young had a diverse repertoire in IL-7Rαhigh but not in IL-7Rαlow cells. These findings suggest that aging affects IL-7Rα 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.