IL-12 reverses the suppressive effect of the CD40 ligand blockade on experimental autoimmune encephalomyelitis (EAE).
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.
Constantinescu
C S
CS
Department of Neurology, University of Pennsylvania, Philadelphia 19104, USA.
Hilliard
B
B
Wysocka
M
M
Ventura
E S
ES
Bhopale
M K
MK
Trinchieri
G
G
Rostami
A M
AM
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
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D008024:Ligands; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D023201:CD40 Ligand; D018664:Interleukin-12