title: CD40 triggering of heterodimeric IL-12 p70 production by dendritic cells in vivo requires a microbial priming signal.
abstract: CD40 ligation triggers IL-12 production by dendritic cells (DC) in vitro. Here, we demonstrate that CD40 cross-linking alone is not sufficient to induce IL-12 production by DC in vivo. Indeed, resting DC make neither the IL-12 p35 nor IL-12 p40 subunits and express only low levels of CD40. Nevertheless, after DC activation by microbial stimuli that primarily upregulate IL-12 p40 and augment CD40 expression, CD40 ligation induces a significant increase in IL-12 p35 and IL-12 p70 heterodimer production. Similarly, IL-12 p70 is produced during T cell activation in the presence but not in the absence of microbial stimuli. Thus, production of bioactive IL-12 by DC can be amplified by T cell-derived signals but must be initiated by innate signals.
authors.affiliation: Immunobiology Laboratory, Imperial Cancer Research Fund, London, United Kingdom.
authors.forename: O
authors.initials: O
authors.lastname: Schulz
authors.forename: A D
authors.initials: AD
authors.lastname: Edwards
authors.forename: M
authors.initials: M
authors.lastname: Schito
authors.forename: J
authors.initials: J
authors.lastname: Aliberti
authors.forename: S
authors.initials: S
authors.lastname: Manickasingham
authors.forename: A
authors.initials: A
authors.lastname: Sher
authors.forename: C
authors.initials: C
authors.lastname: Reis e Sousa
mesh_terms: D016475:3T3 Cells; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000502:physiology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000953:Antigens, Protozoan / Q000008:administration & dosage* / Q000276:immunology*; D019013:CD40 Antigens / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology; D019281:Dimerization; D005260:Female; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000378:metabolism; D007399:Interphase / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D016513:Mice, SCID; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014122:Toxoplasma / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan; D019013:CD40 Antigens; C094052:soluble tachyzoite antigen, Toxoplasma gondii; D018664:Interleukin-12