Published online before print October 1, 2009
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Laboratory of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA
1. Correspondence: Laboratory of Immunology, National Institute on Aging, National Institutes of Health, 251 Bayview Blvd., Suite 100, Baltimore, MD 21224, USA. E-mail: wengn{at}mail.nih.gov
ABSTRACT
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.
Key Words: cytokines • aging
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