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

• Published in: Blood 2000-10, Vol.96 (7), p.2628-2631
• Main Authors: Leverkus, Martin, Walczak, Henning, McLellan, Alex, Fries, Hans-Werner, Terbeck, Gabi, Bröcker, Eva-B., Kämpgen, Eckhart
• Format: Article
• Language: English
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Antigens, CD; Apoptosis; Apoptosis Regulatory Proteins; Biological and medical sciences; Caspase 8; Caspase 9; Caspases - metabolism; CD83 Antigen; Cells, Cultured; Dendritic Cells - chemistry; Dendritic Cells - physiology; Dinoprostone - pharmacology; Drug Resistance; fas Receptor - analysis; fas Receptor - pharmacology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology; Humans; Immunobiology; Immunoglobulins - analysis; Interleukin-1 - pharmacology; Interleukin-4 - pharmacology; Interleukin-6 - pharmacology; Membrane Glycoproteins - analysis; Membrane Glycoproteins - pharmacology; Miscellaneous; Regulatory factors and their cellular receptors; TNF-Related Apoptosis-Inducing Ligand; Tumor Necrosis Factor-alpha - analysis; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V96.7.2628

Dendritic cells (DCs) disappear from lymph nodes 1 to 2 days after antigen presentation, presumably by apoptosis. To evaluate the role of death ligands in elimination of DCs, we analyzed the sensitivity of human DCs to CD95 ligand (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 populations expressed CD95, TRAIL-R2, and TRAIL-R3 at comparable levels, suggesting 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 immature DCs. Thus, death ligand sensitivity proved to be dependent on DC maturation and inversely correlated with expression levels of cFLIP. Induction of apoptosis by TRAIL or CD95L does not seem to play a role in the elimination of mature DCs, but instead might serve to regulate immature DC populations.