期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 87, 期 1, 页码 43-49出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1189/jlb.0209086
关键词
cytokines; aging
资金
- Intramural Research Program of the NIA
- National Cancer Institute
- National Institutes of Health
- NATIONAL INSTITUTE ON AGING [ZIAAG000757, ZICAG000912] Funding Source: NIH RePORTER
An age-related decline in human immune response is marked by the accumulation of CD28(-) CD8 T cells, which is attributed to repeated antigenic stimulation and to homeostatic proliferation mediated by cytokines such as IL-15. However, the identity of the cytokines that are responsible for the maintenance of CD28 expression is less known. Here, we report the role of IL-21 in the regulation of IL-15-mediated growth and CD28 expression of CD8 memory T cells of young and old donors. We showed that IL-21 drives more IL-15-stimulated cells to enter cell division and to undergo apoptosis. Furthermore, IL-21 preferentially enhanced IL-15-induced proliferation of CD28(+) CD8 memory T cells over their CD28(-) counterparts, as CD28(+) cells expressed higher levels of IL-15R and IL-21R and greater pSTAT5 upon IL-15 and IL-21 stimulation. In addition, IL-21 reduced IL-15-induced CD28 down-regulation in CD8 memory T cells. Finally, the ability of proliferation and survival in response to homeostatic cytokines IL-15 and IL-21 of CD28(+) CD8 memory T cells was well-maintained with age. Together, these findings suggest that IL- 21 enhances IL-15-mediated proliferation of CD8 memory T cells, particularly CD28(+) memory T cells, and also serves as an antagonist to the IL-15-induced increase of CD28 CD8 T cells. J. Leukoc. Biol. 87: 43-49; 2010.
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