title: Mice with a disrupted IFN-gamma gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE).
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-gamma, 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-gamma in humans suffering from multiple sclerosis to studies using anti-IFN-gamma Abs in mice with EAE. To study the role of IFN-gamma and IFN-gamma-producing cells in EAE, we crossed IFN-gamma knockout mice (H-2b) (unable to produce IFN-gamma due to the disruption of the IFN-gamma gene) with an EAE-susceptible mouse strain, B10.PL (H-2u). EAE was seen in IFN-gamma knockout mice, heterozygotic (IFN-gamma +/-) mice, as well as wild-type littermates following immunization with MBP. Histologic analyses of the central nervous system of IFN-gamma knockout mice with EAE revealed massive infiltrates composed of lymphocytes, macrophages, and granulocytes. We conclude that the presence of IFN-gamma is not crucial to the induction or the clinical course of EAE.
authors.affiliation: Department of Medicine, Stanford University Medical School, CA 94305, USA.
authors.forename: I A
authors.initials: IA
authors.lastname: Ferber
authors.forename: S
authors.initials: S
authors.lastname: Brocke
authors.forename: C
authors.initials: C
authors.lastname: Taylor-Edwards
authors.forename: W
authors.initials: W
authors.lastname: Ridgway
authors.forename: C
authors.initials: C
authors.lastname: Dinisco
authors.forename: L
authors.initials: L
authors.lastname: Steinman
authors.forename: D
authors.initials: D
authors.lastname: Dalton
authors.forename: C G
authors.initials: CG
authors.lastname: Fathman
mesh_terms: D000818:Animals; D001483:Base Sequence; D004198:Disease Susceptibility / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000235:genetics* / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data
chemical_list: D007371:Interferon-gamma