Ectopic human telomerase catalytic subunit expression maintains telomere length but is not sufficient for CD8+ T lymphocyte immortalization.

Details

Serval ID
serval:BIB_4CB9B9DCFE60
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Ectopic human telomerase catalytic subunit expression maintains telomere length but is not sufficient for CD8+ T lymphocyte immortalization.
Journal
Journal of Immunology
Author(s)
Migliaccio M., Amacker M., Just T., Reichenbach P., Valmori D., Cerottini J.C., Romero P., Nabholz M.
ISSN
0022-1767[print], 0022-1767[linking]
Publication state
Published
Issued date
2000
Volume
165
Number
9
Pages
4978-4984
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Abstract
Like most somatic human cells, T lymphocytes have a limited replicative life span. This phenomenon, called senescence, presents a serious barrier to clinical applications that require large numbers of Ag-specific T cells such as adoptive transfer therapy. Ectopic expression of hTERT, the human catalytic subunit of the enzyme telomerase, permits fibroblasts and endothelial cells to avoid senescence and to become immortal. In an attempt to immortalize normal human CD8(+) T lymphocytes, we infected bulk cultures or clones of these cells with a retrovirus transducing an hTERT cDNA clone. More than 90% of transduced cells expressed the transgene, and the cell populations contained high levels of telomerase activity. Measuring the content of total telomere repeats in individual cells (by flowFISH) we found that ectopic hTERT expression reversed the gradual loss of telomeric DNA observed in control populations during long term culture. Telomere length in transduced cells reached the levels observed in freshly isolated normal CD8(+) lymphocytes. Nevertheless, all hTERT-transduced populations stopped to divide at the same time as nontransduced or vector-transduced control cells. When kept in IL-2 the arrested cells remained alive. Our results indicate that hTERT may be required but is not sufficient to immortalize human T lymphocytes.
Keywords
CD8-Positive T-Lymphocytes/cytology, CD8-Positive T-Lymphocytes/enzymology, Catalytic Domain/genetics, Cell Culture Techniques, Cell Division/genetics, Cell Division/immunology, Cell Line, Transformed, Cell Separation, DNA-Binding Proteins, Humans, Lymphocyte Activation/genetics, RNA, Retroviridae/genetics, Retroviridae/immunology, T-Lymphocytes, Cytotoxic/cytology, T-Lymphocytes, Cytotoxic/enzymology, Telomerase/biosynthesis, Telomerase/genetics, Telomere/metabolism, Transduction, Genetic
Pubmed
Web of science
Create date
28/01/2008 11:13
Last modification date
20/08/2019 14:01
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