1. IL-12 reverses the suppressive effect of the CD40 ligand blockade on experimental autoimmune encephalomyelitis (EAE).
- Author
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Constantinescu CS, Hilliard B, Wysocka M, Ventura ES, Bhopale MK, Trinchieri G, and Rostami AM
- Subjects
- Animals, Antibodies, Monoclonal pharmacology, CD40 Antigens metabolism, CD40 Ligand, Crosses, Genetic, Encephalomyelitis, Autoimmune, Experimental epidemiology, Encephalomyelitis, Autoimmune, Experimental metabolism, Encephalomyelitis, Autoimmune, Experimental prevention & control, Guinea Pigs, Immunity, Cellular, Incidence, Interleukin-12 administration & dosage, Ligands, Membrane Glycoproteins immunology, Mice, Mice, Inbred Strains, Recombinant Proteins administration & dosage, Spinal Cord immunology, Encephalomyelitis, Autoimmune, Experimental immunology, Immunosuppression Therapy, Interleukin-12 immunology, Interleukin-12 pharmacology, Membrane Glycoproteins antagonists & inhibitors, Recombinant Proteins adverse effects
- 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.
- Published
- 1999
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