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

Mol Immunol. 2007 Feb;44(6):1446-53. doi: 10.1016/j.molimm.2006.04.029. Epub 2006 Jun 27.

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).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / immunology*
  • Apoptosis Regulatory Proteins / biosynthesis*
  • Apoptosis Regulatory Proteins / genetics
  • Bcl-2-Like Protein 11
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Humans
  • Interleukin-2 / deficiency*
  • Interleukin-2 / genetics
  • Ligands
  • Lymphocyte Activation*
  • Membrane Proteins / biosynthesis*
  • Membrane Proteins / genetics
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins / metabolism*
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • RNA, Small Interfering / immunology
  • RNA, Small Interfering / metabolism
  • Receptors, Death Domain / immunology
  • Receptors, Death Domain / metabolism*

Substances

  • Apoptosis Regulatory Proteins
  • BCL2L11 protein, human
  • Bcl-2-Like Protein 11
  • Interleukin-2
  • Ligands
  • Membrane Proteins
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Small Interfering
  • Receptors, Death Domain