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The Journal of Immunology, 2008, 180, 3775 -3781
Copyright © 2008 by The American Association of Immunologists, Inc.

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Telomerase Is Involved in IL-7-Mediated Differential Survival of Naive and Memory CD4+ T Cells1

Yinhua Yang, Jie An and Nan-ping Weng2

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

IL-7 plays an essential role in T cell maintenance and survival. The survival effect of IL-7 is thought to be mediated through regulation of Bcl2 family proteins. After a comparative analysis of IL-7-induced growth and cell death of human naive and memory CD4+ T cells, we observed that more memory CD4+ T cells underwent cell division and proceeded to apoptosis than naive cells in response to IL-7. However, IL-7-induced expressions of Bcl2 family members (Bcl2, Bcl-xL, Bax, and Bad) were similar between naive and memory cells. Instead, we found that IL-7 induced higher levels of telomerase activity in naive cells than in memory cells, and the levels of IL-7-induced telomerase activity had a significant inverse correlation with cell death in CD4+ T cells. Furthermore, we showed that reducing expression of telomerase reverse transcriptase and telomerase activity significantly increased cell death of IL-7-cultured CD4+ T cells. Together, these findings demonstrate that telomerase is involved in IL-7-mediated differential survival of naive and memory CD4+ T cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 Y.Y., J.A., and N.-p.W. were supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health.

2 Address correspondence and reprint requests to Dr. Nan-ping Weng, Laboratory of Immunology, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224. E-mail address: Wengn{at}mail.nih.gov

3 Abbreviations used in this paper: TERT, telomerase reverse transcriptase; ANXA5, annexin V; 7-AAD, 7-aminoactinomycin D; hTERT, human TERT; TRAP, telomeric repeat amplification protocol; PI, proliferation index; MFI, mean fluorescent intensity; Acox1, acyl-coenzyme A oxidase 1; sh, small hairpin.







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