Differential sensitivity of Jurkat and primary T cells to caspase-independent cell death triggered upon Fas stimulation.
Fas-induced apoptosis, a key event in the regulation of lymphocyte homeostasis, is mainly mediated by the activation of a cascade of caspases. Using caspase- and Fas-associated death domain protein-deficient Jurkat cell lines as well as a pan-caspase inhibitor (Z-VAD-fmk), we observed a second Fas-induced cell death event, independent of any known caspase activation. This pathway is of slow kinetics and displays some features of necrosis. However, this caspase-independent pathway does not seem to play a significant role in the Fas-mediated death of primary activated T cell blasts. Indeed, in this setting, Fas-induced cell death was always substantially inhibited by Z-VAD-fmk, suggesting that caspase activation is an absolute requirement in the Fas-induced death of primary human T lymphocytes.
Vonarbourg
Cédric
C
INSERM U429, Développement Normal et Pathologique du Système Immunitaire, Hôpital Necker-Enfants Malades, Paris, France.
Stolzenberg
Marie-Claude
MC
Hölzelova
Eliska
E
Fischer
Alain
A
Deist
Françoise Le
FL
Rieux-Laucat
Frédéric
F
D017209:Apoptosis; D020169:Caspases / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D007700:Kinetics; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000502:physiology*; D019014:fas Receptor / Q000502:physiology*
D019014:fas Receptor; D020169:Caspases