title: IL-12 reverses the suppressive effect of the CD40 ligand blockade on experimental autoimmune encephalomyelitis (EAE).
abstract: Blockade of the CD40 ligand (CD40L)-CD40 interaction suppresses experimental autoimmune encephalomyelitis (EAE). Since this interaction induces IL-12, an essential cytokine for EAE induction, we hypothesized that CD40L blockade may suppress EAE through IL-12 inhibition. Here we show that exogenous IL-12 abolishes the ability of anti-CD40L monoclonal antibodies to prevent EAE. Anti-IL-12 antibodies prevent this reversal and protect from EAE. These results show that IL-12 is sufficient to overcome CD40L blockade and suggest that, of the multiple consequences of the CD40L-CD40 interaction, IL-12 induction is an essential one for induction of EAE.
authors.affiliation: Department of Neurology, University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Constantinescu
authors.forename: B
authors.initials: B
authors.lastname: Hilliard
authors.forename: M
authors.initials: M
authors.lastname: Wysocka
authors.forename: E S
authors.initials: ES
authors.lastname: Ventura
authors.forename: M K
authors.initials: MK
authors.lastname: Bhopale
authors.forename: G
authors.initials: G
authors.lastname: Trinchieri
authors.forename: A M
authors.initials: AM
authors.lastname: Rostami
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand; D003433:Crosses, Genetic; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000453:epidemiology / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D006168:Guinea Pigs; D007111:Immunity, Cellular; D007165:Immunosuppression Therapy; D015994:Incidence; D018664:Interleukin-12 / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology*; D008024:Ligands; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects*; D013116:Spinal Cord / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D008024:Ligands; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D023201:CD40 Ligand; D018664:Interleukin-12