Maturation of dendritic cells leads to up-regulation of cellular FLICE-inhibitory protein and concomitant down-regulation of death ligand-mediated apoptosis

Dendritic cells (DCs) disappear from lymph nodes 1 to 2 days after antigen presentation, presumably by apoptosis, To evaluate the role of death ligand s in elimination of DCs, we analyzed the sensitivity of human DCs to CD95 l igand (CD95L) and tumor necrosis factor-related apoptosis-inducing ligand ( TRAIL), We found mature DCs to be resistant to killing via CD95L or TRAIL, whereas only immature DCs were partially sensitive. However, all DC populat ions expressed CD95, TRAIL-R2, and TRAIL-R3 at comparable levels, suggestin g that sensitivity to death ligand-induced DC apoptosis is not regulated at the receptor level. Interestingly, mature DCs highly expressed the caspase 8 Inhibitory protein cFLIP, whereas only low levels were detected in immat ure DCs. Thus, death ligand sensitivity proved to be dependent on DC matura tion and inversely correlated with expression levels of cFLIP, Induction of apoptosis by TRAIL or CD95L does not seem to play a role in the eliminatio n of mature DCs, but instead might serve to regulate immature DC population s. (Blood. 2000;96:2628-2631) (C) 2000 by The American Society of Hematolog y.