Differential involvement of a Fas-CPP32-like protease pathway in apoptosis of TCR/CD9-costimulated, naive T cells and TCR-restimulated, activated T cells

J Immunol. 1998 Jun 15;160(12):5790-6.


Our previous study showed that CD9 costimulation of TCR-triggered naive T cells elicits activation ([3H]TdR incorporation) that is similar to CD28 costimulation; however, unlike CD28 costimulation, CD9 costimulation results in apoptosis of these previously activated T cells. Here, we investigated whether the apoptosis occurring after TCR/CD9 stimulation is associated with a death pathway involving Fas stimulation and Fas-mediated caspase activation as observed in activation-induced cell death (AICD). In contrast to AICD, the apoptosis resulting from TCR/CD9 stimulation in C57BL/6 T cells was independent of Fas, because this form of apoptosis was not prevented by anti-Fas ligand mAb and was also induced in MRL/lpr T cells. AICD was observed at 12 h after the restimulation of activated T cells with anti-CD3 and reached a peak level at 24 h after this restimulation. CPP32-like protease activity was detected during AICD. Although TCR/CD9 stimulation-associated apoptosis was observed at 24 h after the stimulation of naive T cells and reached a peak level at 36 h after this stimulation, CPP32-like protease activity in these T cells was only marginal at all time points. Nevertheless, both forms of apoptosis were prevented similarly by two different peptide-based caspase inhibitors. These results indicate that the apoptosis that follows the T cell activation which is induced as a result of CD9 costimulation does not involve a Fas-CPP32-like protease pathway, but suggest that different caspase members are likely to be critical in this form of apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / immunology*
  • Apoptosis / immunology*
  • Caspase 1
  • Caspase 3
  • Caspases*
  • Cells, Cultured
  • Cysteine Endopeptidases / immunology*
  • Cysteine Proteinase Inhibitors / pharmacology
  • Enzyme Precursors / immunology*
  • Female
  • Lymphocyte Activation*
  • Membrane Glycoproteins*
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Antigen, T-Cell / immunology*
  • T-Lymphocytes / immunology*
  • Tetraspanin 29
  • fas Receptor / immunology*


  • Antigens, CD
  • Cd9 protein, mouse
  • Cysteine Proteinase Inhibitors
  • Enzyme Precursors
  • Membrane Glycoproteins
  • Receptors, Antigen, T-Cell
  • Tetraspanin 29
  • fas Receptor
  • Casp3 protein, mouse
  • Caspase 3
  • Caspases
  • Cysteine Endopeptidases
  • Caspase 1