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Apoptosis by IL-2 deprivation in human CD8+ T cell blasts predominates over death receptor ligation, requires Bim expression and is associated with Mcl-1 loss.
- Source :
-
Molecular immunology [Mol Immunol] 2007 Feb; Vol. 44 (6), pp. 1446-53. Date of Electronic Publication: 2006 Jun 27. - Publication Year :
- 2007
-
Abstract
- The mechanisms responsible for the down-modulation of the activation of separated CD4(+) or CD8(+) human T cell blasts were studied using cells obtained from healthy donors. In the absence of IL-2, human CD4(+) T cell blasts were sensitive to both FasL and Apo2L/TRAIL, but human CD8(+) T cell blasts died, with no additional effect of death receptor ligation. CD8(+) T cell blasts were more sensitive than CD4(+) T cell blasts to apoptosis induction by IL-2 deprivation, which was associated with a decrease in the expression of anti-apoptotic proteins of the Bcl-2 family, especially of Mcl-1 in CD8(+) T cell blasts. The maintenance of high levels of Bim expression was also necessary, since down-modulation of Bim expression by siRNA in normal human CD8(+) T cell blasts greatly reduced apoptosis by IL-2 deprivation. These data, together with previous works, point to an important role of the presence or absence of immuno-stimulatory cytokines in the type of regulation of human CD8(+) T cell responses (death by cytokine deprivation versus death receptor inhibition of cytokine-dependent growth).
- Subjects :
- Apoptosis Regulatory Proteins genetics
Bcl-2-Like Protein 11
CD4-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes metabolism
Cells, Cultured
Humans
Interleukin-2 genetics
Ligands
Membrane Proteins genetics
Myeloid Cell Leukemia Sequence 1 Protein
Proto-Oncogene Proteins genetics
RNA, Small Interfering immunology
RNA, Small Interfering metabolism
Receptors, Death Domain immunology
Apoptosis immunology
Apoptosis Regulatory Proteins biosynthesis
CD8-Positive T-Lymphocytes cytology
CD8-Positive T-Lymphocytes immunology
Interleukin-2 deficiency
Lymphocyte Activation
Membrane Proteins biosynthesis
Neoplasm Proteins metabolism
Proto-Oncogene Proteins biosynthesis
Proto-Oncogene Proteins c-bcl-2 metabolism
Receptors, Death Domain metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0161-5890
- Volume :
- 44
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Molecular immunology
- Publication Type :
- Academic Journal
- Accession number :
- 16806475
- Full Text :
- https://doi.org/10.1016/j.molimm.2006.04.029