What transgenic and knockout mouse models teach us about experimental autoimmune encephalomyelitis.
Multiple sclerosis (MS) is a disease of the central nervous system with presumed autoimmune etiology. Experimental autoimmune encephalomyelitis (EAE), an inducible autoimmune disease in laboratory animals, is a widely accepted animal model of MS. Although it is well known that EAE is induced by autoreactive CD4+ T cells specific for myelin antigens, the demyelination process is manifested as a result of complex interactions among encephalitogenic, regulatory and accessory cell populations and factors produced by these cells. The outcome of the disease depends on which components become dominant. Examination of these components using genetically manipulated transgenic or gene-disrupted animal models has proved to be very useful. Here we examine the main processes leading to the development of EAE. The participation of different lymphocyte populations such as T, B cells or NK cells, as well as regulatory molecules and cytokines in the induction and regulation of EAE is discussed in the light of transgenic and knockout animal experiments. These animal models clearly show that autoimmune processes are regulated in a complex way, and that a given factor in this regulation can have very different effects according to the given microenvironment in which it acts.
Fazekas
G
G
Division of Demyelinating Disease and Aging, National Institute of Neuroscience, Tokyo, Japan.
Tabira
T
T
D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000954:Antigens, Surface; D016207:Cytokines; D011948:Receptors, Antigen, T-Cell