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Prepublished online as a Blood First Edition Paper on April 10, 2003; DOI 10.1182/blood-2002-07-2015. This Article Full Text (PDF) All Versions of this Article: 2002-07-2015v1 102/3/849    most recent Alert me when this article is cited Alert me if a correction is posted 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 Roeth, A. Articles by Luiten, R. M Search for Related Content PubMed PubMed Citation Articles by Roeth, A. Articles by Luiten, R. M Social Bookmarking                   What's this? Submitted July 8, 2002 Accepted April 2, 2003 Telomerase levels control the life span of human T lymphocytes Alexander Roeth, Hans Yssel, Jerome Pene, Elizabeth A Chavez, Mike Schertzer, Peter M Lansdorp, Hergen Spits*, and Rosalie M Luiten Terry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada INSERM U454, Montpellier, France Immunology, The Netherlands Cancer Institute / Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; Cell Biology & Histology AMC, University of Amsterdam, Amsterdam, The Netherlands Immunology, The Netherlands Cancer Institute / Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands * Corresponding author; email: hergen.spits{at}amc.uva.nl. The loss of telomeric DNA with each cell division contributes to the limited replicative life span of human T lymphocytes. Although telomerase is transiently expressed in T lymphocytes upon activation, it is insufficient to confer immortality. We have shown previously that immortalization of human CD8+ T lymphocytes can be achieved by ectopic expression of the hTERT gene, which encodes for the catalytic component of the telomerase complex. To study the role of endogenous hTERT in the life span of human T cells, we blocked endogenous hTERT expression by ectopic expression of dominant-negative (DN) hTERT. Cells expressing DN-hTERT had a decreased life span and showed cytogenetic abnormalities, including chromosome ends without detectable telomeric DNA as well as chromosome fusions. These results indicate that while endogenous hTERT cannot prevent overall telomere shortening, it has a major influence on the longevity of human T cells. Furthermore, we show that upregulation of hTERT in T cells upon activation decreases over time in culture. Long-term cultured T cells also show a decreased expression of c-myc upon activation, resulting in less c-myc-induced transcription of hTERT. 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