Changes in telomerase activity and telomere length during human T lymphocyte senescence.
It has been proposed that telomeres shorten with every cell cycle because the normal mechanism of DNA replication cannot replicate the end sequences of the lagging DNA strand. Telomerase, a ribonucleoprotein enzyme that synthesizes telomeric DNA repeats at the DNA 3' ends of eukaryotic chromosomes, can compensate for such shortening, by extending the template of the lagging strand. Telomerase activity has been identified in human germline cells and in neoplastic immortal somatic cells, but not in most normal somatic cells, which senesce after a certain number of cell divisions. We and others have found that telomerase activity is present in normal human lymphocytes and is upregulated when the cells are activated. But, unlike the immortal cell lines, presence of telomerase activity is not sufficient to make T cells immortal and telomeres from these cells shorten continuously during in vitro culture. After senescence, telomerase activity, as detected by the TRAP technique, was downregulated. A cytotoxic T lymphocyte (CTL) cell line that was established in the laboratory has very short terminal restriction fragments (TRFs). Telomerase activity in this cell line is induced during activation and this activity is tightly correlated with cell proliferation. The level of telomerase activity in activated peripheral blood T cells, the CTL cell line, and two leukemia cell lines does not correlate with the average TRF length, suggesting that other factors besides telomerase activity are involved in the regulation of telomere length.
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Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University at Chicago, Maywood, Illinois 60153, USA.
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D000328:Adult; D002453:Cell Cycle; D002455:Cell Division; D002478:Cells, Cultured; D016922:Cellular Senescence; D004261:DNA Replication; D004790:Enzyme Induction; D005260:Female; D018922:HL-60 Cells / Q000166:cytology / Q000201:enzymology / Q000648:ultrastructure; D006801:Humans; D008297:Male; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D016133:Polymerase Chain Reaction; D012091:Repetitive Sequences, Nucleic Acid; D013601:T-Lymphocytes / Q000166:cytology* / Q000201:enzymology / Q000648:ultrastructure; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000201:enzymology / Q000648:ultrastructure; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000648:ultrastructure*; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; D019098:Telomerase