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Brief Definitive Report

FAS Engagement Induces the Maturation of Dendritic Cells (Dcs), the Release of Interleukin (Il)-1β, and the Production of Interferon in the Absence of IL-12 during Dc–T Cell Cognate Interaction

Maria Rescigno^a, Vincent Piguet^b, Barbara Valzasina^a, Suzanne Lens^c, Rudolf Zubler^d, Lars French^b, Vincent Kindler^d, Jurg Tschopp^c, and Paola Ricciardi-Castagnoli^a

^a Department of Biotechnology and Bioscience, University of Milano-Bicocca, 20126 Milan, Italy
^b Department of Dermatology, Hôspitaux Universitaires de Genéve, Département Hospitalo-Universitaire Romand de Dermatologie et Vénéréologie, CH-1211 Geneva, Switzerland
^c Institut de Biochimie, University of Lausanne, CH-1066 Epalinges, Switzerland
^d Division of Hematology, Hôspitaux Universitaires Vaudois et Genevois, CH-1211 Geneva, Switzerland
Department of Biotechnology and Bioscience, University of Milano-Bicocca, 20126 Milan, Italy.39-02-644-8356539-02-644-83559

paola.castagnoli{at}unimib.it

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 susceptible to Fas-induced cell death. This resistance correlates with the constitutive expression of the Fas-associated death domain–like IL-1β–converting enzyme (FLICE)-inhibitory protein (FLIP) ligand. We demonstrate a new role of Fas in DC physiology. Engagement of Fas on immature DCs by Fas ligand (FasL) or by anti-Fas antibodies induces the phenotypical and functional maturation of primary DCs. Fas-activated DCs upregulate the expression of the major histocompatibility complex class II, B7, and DC–lysosome-associated membrane protein (DC-LAMP) molecules and secrete proinflammatory cytokines, in particular interleukin (IL)-1β and tumor necrosis factor . Mature DCs, if exposed to FasL, produce even higher amounts of IL-1β. Importantly, it is possible to reduce the production of IL-1β and interferon (IFN)- during DC–T cell interaction by blocking the coupling of Fas–FasL with 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 Fas-induced, IFN- secretion is independent of IL-12.

Key Words: dendritic cells • Fas • interleukin 1β • FLIP • interferon

© 2000 The Rockefeller University Press

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