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The Journal of Immunology, 2005, 174: 4019-4024.
Copyright © 2005 by The American Association of Immunologists

IL-15 Activates Telomerase and Minimizes Telomere Loss and May Preserve the Replicative Life Span of Memory CD8+ T Cells In Vitro

Yu Li1, Wang Zhi1, Przemyslaw Wareski and Nan-ping Weng2

Laboratory of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224

The preservation of the replicative life span of memory CD8+ T cells is vital for long-term immune protection. Although IL-15 plays a key role in the homeostasis of memory CD8+ T cells, it is unknown whether IL-15 regulates the replicative life span of memory CD8+ T cells. In this study, we report an analysis of telomerase expression and telomere length in human memory phenotype CD8+ T cells maintained by IL-15 in vitro. We demonstrate that IL-15 is capable of activating telomerase in memory CD8+ T cells via Jak3 and PI3K signaling pathways. Furthermore, IL-15 induces a sustained level of telomerase activity over long periods of time, and in turn minimizes telomere loss in memory CD8+ T cells after substantial cell divisions. These findings suggest that IL-15 activates stable telomerase expression and compensates telomere loss in memory phenotype CD8+ T cells, and that telomerase may play an important role in memory CD8+ T cell homeostasis.




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