Mice with a disrupted IFN-gamma gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE).
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.
Ferber
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IA
Department of Medicine, Stanford University Medical School, CA 94305, USA.
Brocke
S
S
Taylor-Edwards
C
C
Ridgway
W
W
Dinisco
C
C
Steinman
L
L
Dalton
D
D
Fathman
C G
CG
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
D007371:Interferon-gamma