Differential susceptibility to CD95 (Apo-1/Fas) and MHC class II-induced apoptosis during murine dendritic cell development

Disappearance of antigen presenting cells (APC) from the lymph node occurs following antigen specific interactions with T eel Is. We have investigated the regulation of CD95 (Apo-1/Fas) induced apoptosis during murine dendrit ic cell (DC) development Consistent with the moderate levels of CD95 surfac e expression and low, or absent, MHC class II expression, immature DC in bo ne marrow cultures were highly sensitive to CD95 induced apoptosis, but ins ensitive to class II mediated apoptosis, In contrast, mature splenic, epide rmal and bone marrow derived DC were fully resistant to CD95 induced cell d eath, but sensitive to class It induced apoptosis, Although caspase 3 and 8 activation was detected in immature DC undergoing CD95L-induced apoptosis, the pan-caspase inhibitor zVAD-fmk did not inhibit the early events of CD9 5-induced mitochondrial depolarisation or phosphatidyl serine exposure and only partially inhibited the killing of immature DC. In contrast, zVAD-fmk was completely effective in preventing CD95L mediated death of murine thymo cytes, Collectively, these data do not support a major role of CD95: CD95L ligation in apoptosis of mature DC, but rather emphasise the existence of d istinct pathways for the elimination of DC at different stages of maturatio n.