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

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) high and 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 low CD8 T cells, leading to decreased STAT5 phosphorylation and survival responses to IL-7 compared with young subjects (40 years and younger). These EM CD45RA IL-7R low cells were largely antigen experienced (CD27 CD28 ), replicatively senescent (CD57 ), and perforinhigh CD8 T cells that had decreased IL-7R mRNA, independent of guanine and adenine binding protein (GABP ) 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 high and IL-7R low cells, whereas the young had a diverse repertoire in IL-7R high but not in IL-7R low cells. These findings suggest that aging affects IL7R 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 EM CD45RA CD8 T cells with a diverse TCR repertoire in the young but not in the elderly. (Blood. 2006;107:2855-2862)