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 Blood, 1 April 2006, Vol. 107, No. 7, pp. 2855-2862.
Prepublished online as a Blood First Edition Paper on December 15, 2005; DOI 10.1182/blood-2005-09-3560.

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IMMUNOBIOLOGY

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

Hang-Rae Kim, Myung Sun Hong, Jin Myung Dan, and Insoo Kang

From the Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT.

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+ IL-7R{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 perforinhigh 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-7R{alpha}high but not in IL-7R{alpha}low cells. These findings suggest that aging affects IL-7R{alpha} 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.


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