Bcl-2, Bcl-xL and c-FLIPL potentially regulate the susceptibility of human peripheral blood monocyte-derived dendritic cells to cell death at different developmental stages

We examined the susceptibility of human monocyte-derived dendritic cells (DCs) to spontaneous and CD95-mediated cell death at different developmental stages. Time course experiments revealed that the susceptibility of mature dendritic cells (mDCs) to spontaneous cell death was significantly lower than that of immature dendritic cells (iDCs) in a long-term culture under cytokine-free conditions, and the treatment with GM-CSF rescued these cells from spontaneous cell death at the late culture period. iDCs and mDCs expressed similar levels of CD95 whereas both cell types were relatively resistant to CD95-mediated cell death. Antigen (Ag)-specific and nonspecific cognate interaction with T cells failed to cause cell death of iDCs and mDCs. iDCs constitutively expressed transcripts and intracellular products of Bcl-2 and Bcl-xL, but not cellular FLICE-inhibitory proteinlong (c-FLIPL), while the increased expressions of Bcl-2, Bcl-xL and c-FLIPL were observed in mDCs. These results suggest that the selective expressions of Bcl-2, Bcl-xL and c-FLIPL may be involved in the difference in the susceptibility to cell death between iDCs and mDCs.