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The Journal of Immunology, 2000, 165: 4239-4245.
Copyright © 2000 by The American Association of Immunologists

Immortalization of Human CD8+ T Cell Clones by Ectopic Expression of Telomerase Reverse Transcriptase1

Erik Hooijberg2,*, Janneke J. Ruizendaal2,*, Peter J. F. Snijders{dagger}, Esther W. M. Kueter*, Jan M. M. Walboomers{dagger} and Hergen Spits3,*

* Department of Immunology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, and {dagger} Department of Pathology, Section Molecular Pathology, University Hospital Free University, Amsterdam, The Netherlands

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.




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