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Prepublished online as a Blood First Edition Paper on February 13, 2003; DOI 10.1182/blood-2002-07-2018. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-07-2018v1 101/11/4512    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Luiten, R. M. Articles by Spits, H. Search for Related Content PubMed PubMed Citation Articles by Luiten, R. M. Articles by Spits, H. Related Collections Immunobiology Apoptosis Immunotherapy Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 June 2003, Vol. 101, No. 11, pp. 4512-4519 IMMUNOBIOLOGY Ectopic hTERT expression extends the life span of human CD4+ helper and regulatory T-cell clones and confers resistance to oxidative stress–induced apoptosis Rosalie M. Luiten, Jérôme Pène, Hans Yssel, and Hergen Spits From The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; and the Institut National de la Santé et de la Recherche Médicale (INSERM) U454, Montpellier, France. Human somatic cells have a limited life span in vitro. Upon aging and with each cell division, shortening of telomeres occurs, which eventually will lead to cell cycle arrest. Ectopic hTERT expression has been shown to extend the life span of human T cells by preventing this telomere erosion. In the present study, we have shown that ectopic hTERT expression extends the life span of CD4+ T helper type 1 or 2 and regulatory T-cell clones and affected neither the in vitro cytokine production profile nor their specificity for antigen. In mixed cell cultures, ectopic hTERT-expressing clones were found to expand in greater numbers than untransduced cells of the same replicative age. This ectopic hTERT-induced growth advantage was not due to an enhanced cell division rate or number of divisions following T-cell receptor–mediated activation, as determined in carboxyfluorescein diacetate succinimidyl ester (CFSE)–labeling experiments. Moreover, the susceptibility to activation-induced cell death of both cell types was similar. However, cultures of resting hTERT-transduced T cells contained higher frequencies of Bcl-2–expressing cells and lower active caspase-3–expressing cells, compared with wild-type cells. Furthermore, hTERT-transduced cells were more resistant to oxidative stress, which causes preferential DNA damage in telomeres. Taken together, these results show that ectopic hTERT expression not only protects proliferating T cells from replicative senescence but also confers resistance to apoptosis induced by oxidative stress. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Fujii, L. Shao, I. Colmegna, J. J. Goronzy, and C. M. Weyand Telomerase insufficiency in rheumatoid arthritis PNAS, March 17, 2009; 106(11): 4360 - 4365. [Abstract] [Full Text] [PDF] J. Lee, R. Reddy, L. Barsky, J. Scholes, H. Chen, W. Shi, and B. Driscoll Lung alveolar integrity is compromised by telomere shortening in telomerase-null mice Am J Physiol Lung Cell Mol Physiol, January 1, 2009; 296(1): L57 - L70. [Abstract] [Full Text] [PDF] Y. Yang, J. An, and N.-p. 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