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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens / physiology
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CD8-Positive T-Lymphocytes / enzymology*
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CD8-Positive T-Lymphocytes / immunology*
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Cell Culture Techniques / methods
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Cell Line
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Cell Line, Transformed / enzymology*
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Cell Line, Transformed / immunology*
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Cell Survival / genetics
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Cell Survival / immunology
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Clone Cells / enzymology
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Clone Cells / immunology
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Cytokines / physiology
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DNA-Binding Proteins
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Enzyme Activation / genetics
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Enzyme Activation / immunology
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Enzyme Stability / genetics
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Enzyme Stability / immunology
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Epitopes, T-Lymphocyte / analysis
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Epitopes, T-Lymphocyte / immunology
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Gene Expression Regulation / immunology
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Humans
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Immunophenotyping
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Interleukin-7 / biosynthesis
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Interleukin-7 / genetics
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Lymphocyte Activation / genetics*
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Monophenol Monooxygenase / immunology
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Protein Engineering / methods
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RNA*
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RNA, Messenger / biosynthesis
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Telomerase / biosynthesis*
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Telomerase / genetics*
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Telomere / enzymology
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Telomere / genetics
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Transduction, Genetic
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Tumor Cells, Cultured
Substances
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Antigens
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Cytokines
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DNA-Binding Proteins
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Epitopes, T-Lymphocyte
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Interleukin-7
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RNA, Messenger
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telomerase RNA
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RNA
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Monophenol Monooxygenase
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Telomerase