Differential involvement of a Fas-CPP32-like protease pathway in apoptosis of TCR/CD9-costimulated, naive T cells and TCR-restimulated, activated T cells.
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.
Park
C S
CS
Biomedical Research Center, Osaka University Medical School, Suita, Japan.
Yashiro
Y
Y
Tai
X G
XG
Toyo-oka
K
K
Hamaoka
T
T
Yagita
H
H
Okumura
K
K
Neben
S
S
Fujiwara
H
H
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology*; D020170:Caspase 1; D053148:Caspase 3; D020169:Caspases; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000276:immunology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004792:Enzyme Precursors / Q000276:immunology*; D005260:Female; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D060245:Tetraspanin 29; D019014:fas Receptor / Q000276:immunology*
D015703:Antigens, CD; C554870:Cd9 protein, mouse; D015853:Cysteine Proteinase Inhibitors; D004792:Enzyme Precursors; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D060245:Tetraspanin 29; D019014:fas Receptor; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; D020170:Caspase 1