title: Immortalization of human CD8+ T cell clones by ectopic expression of telomerase reverse transcriptase.
abstract: Replicative senescence of T cells is correlated with erosion of telomere ends. Telomerase plays a key role in maintaining telomere length. Therefore, it is thought that telomerase regulates the life span of T cells. To test this hypothesis, we have over-expressed human telomerase reverse transcriptase in human CD8(+) T cells. Ectopic expression of human telomerase reverse transcriptase led to immortalization of these T cells, without altering the phenotype and without loss of specificity or functionality. As the T cells remained dependent on cytokines and Ag stimulation for their in vitro expansion, we conclude that immortalization was achieved without malignant transformation.
authors.affiliation: Department of Immunology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital. erik.hooijberg@azvu.nl
authors.forename: E
authors.initials: E
authors.lastname: Hooijberg
authors.forename: J J
authors.initials: JJ
authors.lastname: Ruizendaal
authors.forename: P J
authors.initials: PJ
authors.lastname: Snijders
authors.forename: E W
authors.initials: EW
authors.lastname: Kueter
authors.forename: J M
authors.initials: JM
authors.lastname: Walboomers
authors.forename: H
authors.initials: H
authors.lastname: Spits
mesh_terms: D000941:Antigens / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology* / Q000276:immunology*; D018929:Cell Culture Techniques / Q000379:methods; D002460:Cell Line; D002461:Cell Line, Transformed / Q000201:enzymology* / Q000276:immunology*; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002999:Clone Cells / Q000201:enzymology / Q000276:immunology; D016207:Cytokines / Q000502:physiology; D004268:DNA-Binding Proteins; D004789:Enzyme Activation / Q000235:genetics / Q000276:immunology; D004795:Enzyme Stability / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000032:analysis / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D015851:Interleukin-7 / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics*; D014442:Monophenol Monooxygenase / Q000276:immunology; D015202:Protein Engineering / Q000379:methods; D012313:RNA; D012333:RNA, Messenger / Q000096:biosynthesis; D019098:Telomerase / Q000096:biosynthesis* / Q000235:genetics*; D016615:Telomere / Q000201:enzymology / Q000235:genetics; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D000941:Antigens; D016207:Cytokines; D004268:DNA-Binding Proteins; D018984:Epitopes, T-Lymphocyte; D015851:Interleukin-7; D012333:RNA, Messenger; C422952:telomerase RNA; D012313:RNA; D014442:Monophenol Monooxygenase; D019098:Telomerase