Mechanisms that limit the in vitro proliferative potential of human CD8+ T lymphocytes.

Details

Serval ID
serval:BIB_37925
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Mechanisms that limit the in vitro proliferative potential of human CD8+ T lymphocytes.
Journal
Journal of Immunology
Author(s)
Migliaccio M., Raj K., Menzel O., Rufer N.
ISSN
0022-1767
Publication state
Published
Issued date
2005
Peer-reviewed
Oui
Volume
174
Number
6
Pages
3335-3343
Language
english
Abstract
Human T lymphocytes can be numerically expanded in vitro only to a limited extent. The cyclin-dependent kinase inhibitor p16(INK4a) is essential in the control of cellular proliferation, and its expression, in epithelial cells, is associated with irreversible growth arrest. Using long-term cultured CD8+ T lymphocytes, we have investigated the role of the p16/pRb pathway in the regulation of T cell proliferation and senescence. In this study, we describe at least two mechanisms that cause replicative growth arrest in cultured lymphocytes. The first one depends on the expression of p16(INK4a) and is directly responsible for the exit of a significant proportion of CD8+ T cells from the proliferative population. This induced p16 expression pattern is observed during each round of mitogen stimulation and is not related to activation-induced cell death. Importantly, knocking down p16(INK4a) expression allows increased proliferation of T cells. The second one is a phenomenon that resembles human fibroblast senescence, but is independent of p16(INK4a) and of telomere attrition. Interestingly, virtually all pRb proteins in the senescent population are found in the active form. Our data indicate that newly synthesized p16(INK4a) limits the proliferation of T lymphocytes that respond to mitogen, but is not required for the loss of mitogen responsiveness called senescence.
Keywords
Base Sequence, CD8-Positive T-Lymphocytes/cytology, CD8-Positive T-Lymphocytes/drug effects, Cell Aging, Cell Cycle, Cell Division, Cells, Cultured, Cyclin-Dependent Kinase Inhibitor p16/genetics, Cyclin-Dependent Kinase Inhibitor p16/metabolism, Genes, p16, Humans, Lymphocyte Activation, Mitogens/pharmacology, RNA, Small Interfering/genetics, Retinoblastoma Protein/metabolism, Telomere/genetics
Pubmed
Web of science
Create date
19/11/2007 12:36
Last modification date
20/08/2019 13:26
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