MICE WITH A DISRUPTED IFN-GAMMA GENE ARE SUSCEPTIBLE TO THE INDUCTIONOF EXPERIMENTAL AUTOIMMUNE ENCEPHALOLMYELITIS (EAE)

Experimental autoimmune encephalomyelitis (EAE), an animal model for m ultiple sclerosis, is an autoimmune disorder seen in mice and rats fol lowing immunization with myelin basic protein (MBP) or MBP-derived pep tides. IFN-gamma, a cytokine produced by a variety of cells, is involv ed in many inflammatory and immune regulatory events. Contradictory re sults concerning exacerbation and the disease course were seen compari ng injections of IFN-gamma in humans suffering from multiple sclerosis to studies using anti-IFN-gamma Abs in mice with EAE. To study the ro le of IFN-gamma and IFN-gamma-producing cells in EAE, we crossed IFN-g amma knockout mice (H-2(b)) (unable to produce IFN-gamma due to the di sruption of the IFN-gamma gene) with an EAE-susceptible mouse strain, B10.PL (H-2(u)). EAE was seen in IFN-gamma knockout mice, heterozygoti c (IFN-gamma(+/-)) mice, as well as wild-type littermates following im munization with MBP. Histologic analyses of the central nervous system of IFN-gamma knockout mice with EAE revealed massive infiltrates comp osed of lymphocytes, macrophages, and granulocytes, We conclude that t he presence of IFN-gamma is not crucial to the induction or the clinic al course of EAE.