Fas engagement induces the maturation of dendritic cells (DCs), the release of interleukin (IL)-1 beta, and the production of interferon gamma in theabsence of IL-12 during DC-T cell cognate interaction: A new role for Fas ligand in inflammatory responses

Ligation of the Fas (CD95) receptor leads to an apoptotic death signal in T cells, B cells, and macrophages. However, human CD34(+)-derived dendritic cells (DCs) and mouse DCs, regardless of their maturation state, are not su sceptible to Fas-induced cell death domain-like IL-1 beta -converting enzym e (FLICE)-inhibitory protein (FLIP) ligand. We demonstrate a new role of Fa s in DC physiology. Engagement of Fas on immature DCs by Fas ligand (FasL) or by anti-Fas antibodies induces the phenotypical and functional maturatio n of primary DCs. Fas-activated DCs upregulate the expression of the major histocompatibility complex class II, B7, and DC-lysosome-associated membran e protein (DC-LAMP) molecules and secrete proinflammatory cytokines, in par ticular interleukin (IL)-1 beta and tumor necrosis factor alpha. Mature DCs , if exposed to FasL, produce even higher amounts of IL-1 beta. Importantly , it is possible to reduce the production of IL-1 beta and interferon (IFN) -gamma during DC-T cell interaction by blocking the coupling of Fas-FasL wi th a Fas competitor. Finally, during cognate DC-T cell recognition, IL-12 ( p70) could not be detected at early or late time points, indicating that Fa s-induced, IFN-gamma secretion is independent of IL-12.