Distinct mechanisms control human naive and antigen-experienced CD8+ T lymphocyte proliferation.

Details

Serval ID
serval:BIB_699A2A6AC48B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Distinct mechanisms control human naive and antigen-experienced CD8+ T lymphocyte proliferation.
Journal
Journal of immunology
Author(s)
Migliaccio M., Alves P.M., Romero P., Rufer N.
ISSN
0022-1767
Publication state
Published
Issued date
2006
Peer-reviewed
Oui
Volume
176
Number
4
Pages
2173-2182
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Human Ag-specific CD8(+) T lymphocytes are heterogeneous and include functionally distinct populations. In this study, we report that at least two distinct mechanisms control the expansion of circulating naive, memory, and effector CD8(+) T lymphocytes when exposed to mitogen or Ag stimulation. The first one leads to apoptosis and occurs shortly after in vitro stimulation. Susceptibility to cell death is prominent among primed T cell subsets, and it is inversely correlated with the size of the ex vivo Bcl-2(high) population within these subsets. Importantly, the Bcl-2(high) phenotype is associated to the proportion of responsive CD8(+) T cells, independently of their differentiation stage. The second one depends on the expression of newly synthesized cyclin-dependent kinase inhibitor p16(INK4a) that occurs in a significant fraction of T cells that had been actively cycling, leading to their cell cycle arrest upon stimulation. Strikingly, accumulation of p16(INK4a) protein preferentially occurs in naive as opposed to primed derived T lymphocytes and is not related to apoptosis. Significant levels of p16 are readily detectable in a small number of ex vivo CD8(+) T cells. Our observations reveal that activation-induced p16 expression represents an alternative process to apoptosis, limiting the proliferation potential of activated naive derived T lymphocytes.
Keywords
Adult, Antigens/immunology, CD8-Positive T-Lymphocytes/cytology, CD8-Positive T-Lymphocytes/immunology, Cell Differentiation, Cell Proliferation, Cells, Cultured, Humans, Immunologic Memory/immunology, Kinetics, Proto-Oncogene Proteins c-bcl-2/metabolism
Pubmed
Web of science
Create date
28/01/2008 12:28
Last modification date
20/08/2019 15:24
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