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This Article Full Text Full Text (PDF) 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 Rufer, N. Articles by Lansdorp, P. M. Search for Related Content PubMed PubMed Citation Articles by Rufer, N. Articles by Lansdorp, P. M. Related Collections Immunobiology Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 August 2001, Vol. 98, No. 3, pp. 597-603 GENE THERAPY Transfer of the human telomerase reverse transcriptase (TERT) gene into T lymphocytes results in extension of replicative potential Nathalie Rufer, Marco Migliaccio, Jennifer Antonchuk, R. Keith Humphries, Eddy Roosnek, and Peter M. Lansdorp From the Division of Immunology and Allergology, University of Geneva, Geneva, Switzerland; Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, CHUV, Lausanne, Switzerland; Swiss Institute for Experimental Cancer Research, Epalinges, Switzerland; Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, Canada; and the Department of Medicine, University of British Columbia, Vancouver, Canada. In most human somatic cells telomeres progressively shorten with each cell division eventually leading to chromosomal instability and cell senescence. The loss of telomere repeats with cell divisions may also limit the replicative life span of antigen-specific T lymphocytes. Recent studies have shown that the replicative life span of various primary human cells can be prolonged by induced expression of the telomerase reverse transcriptase (hTERT) gene. To test whether introduction of hTERT can extend the life span of primary human T lymphocytes, naive CD8+ T lymphocytes were transfected with retroviral vectors containing the hTERT gene. Transduced T-cell clones expressed high levels of telomerase and either maintained or elongated their telomere lengths upon culture for extended periods of time. Two of the transduced subclones retained a normal cloning efficiency for more than 170 population doublings (PDs). In contrast, T-cell clones transfected with control vectors exhibited progressive telomere length shortening and stopped proliferation at around 108 PDs. Telomerase-positive T clones had a normal 46,XY karyotype, maintained their cytotoxic properties, and showed very little staining for the apoptotic marker annexin-V. These results indicate that ectopic hTERT gene expression is capable of extending the replicative life span of primary human CD8+ cytotoxic T lymphocytes. © 2001 by The American Society of Hematology.   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] A. L. Putnam, T. M. Brusko, M. R. Lee, W. Liu, G. L. Szot, T. Ghosh, M. A. Atkinson, and J. A. Bluestone Expansion of Human Regulatory T-Cells From Patients With Type 1 Diabetes Diabetes, March 1, 2009; 58(3): 652 - 662. [Abstract] [Full Text] [PDF] T. Ando, K. Mimura, C. C. Johansson, M. G. Hanson, D. Mougiakakos, C. Larsson, T. Martins da Palma, D. Sakurai, H. Norell, M. Li, et al. 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