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

Détails

ID Serval
serval:BIB_4CB9B9DCFE60
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Ectopic human telomerase catalytic subunit expression maintains telomere length but is not sufficient for CD8+ T lymphocyte immortalization.
Périodique
Journal of Immunology
Auteur(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]
Statut éditorial
Publié
Date de publication
2000
Volume
165
Numéro
9
Pages
4978-4984
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Résumé
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.
Mots-clé
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
Création de la notice
28/01/2008 11:13
Dernière modification de la notice
20/08/2019 14:01
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