Immortalization of human CD8+ T cell clones by ectopic expression of telomerase reverse transcriptase.
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.
Hooijberg
E
E
Department of Immunology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital. erik.hooijberg@azvu.nl
Ruizendaal
J J
JJ
Snijders
P J
PJ
Kueter
E W
EW
Walboomers
J M
JM
Spits
H
H
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
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