NEUTRALIZING ANTIBODIES TO IFN-GAMMA-INDUCING FACTOR PREVENT EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

Specific oligonucleotide primers were used to identify and isolate IFN -gamma-inducing factor (IGIF) from the brain of rats with developing e xperimental autoimmune encephalomyelitis (EAE), a T cell-mediated auto immune disease of the central nervous system that serves as a model fo r multiple sclerosis, IGIF was highly transcribed in the brain at the onset and during the course of active EAE. PCR products encoding rat I GIF were used to generate the recombinant protein that was used to ind uce anti-IGIF neutralizing Abs, These Abs significantly reduced the pr oduction of IFN-gamma by primed T cells proliferating in response to t heir target myelin basic protein epitope and by Con A-activated T cell s from naive donors. When administered to rats during the development of either active or transferred EAE, these Abs significantly blocked t he development of disease, Splenic T cells from protected rats were cu ltured with the encephalitogenic myelin basic protein epitope and eval uated For production of IL-4 and IFN-gamma, These cells, which prolife rated, exhibited a profound increase in IL-4 production that was accom panied by a significant decrease in IFN-gamma and TNF-alpha production . Thus, we suggest that perturbation of the Th1/Th2 balance toward Th2 cells is the mechanism underlying EAE blockade by anti-IGIF immunothe rapy.