Mice with a disrupted IFN-γ gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE)

Abstract

Abstract Experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, is an autoimmune disorder seen in mice and rats following immunization with myelin basic protein (MBP) or MBP-derived peptides. IFN-γ, a cytokine produced by a variety of cells, is involved in many inflammatory and immune regulatory events. Contradictory results concerning exacerbations and the disease course were seen comparing injections of IFN-γ in humans suffering from multiple sclerosis to studies using anti-IFN-γ Abs in mice with EAE. To study the role of IFN-γ and IFN-γ-producing cells in EAE, we crossed IFN-γ knockout mice (H-2b) (unable to produce IFN-γ due to the disruption of the IFN-γ gene) with an EAE-susceptible mouse strain, B10.PL (H-2u). EAE was seen in IFN-γ knockout mice, heterozygotic (IFN-γ +/-) mice, as well as wild-type littermates following immunization with MBP. Histologic analyses of the central nervous system of IFN-γ knockout mice with EAE revealed massive infiltrates composed of lymphocytes, macrophages, and granulocytes. We conclude that the presence of IFN-γ is not crucial to the induction or the clinical course of EAE.