Role of Fas--FasL interactions in the pathogenesis and regulation of autoimmune demyelinating disease.
Multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) represent complex processes that lead to destruction of oligodendrocytes (ODCs) and myelin. T cells are integral to the development of these diseases, but whether T cell-mediated cytolytic mechanisms are involved in the destruction of MHC Class II-negative targets, such as oligodendroglia and myelin, in the CNS is unclear. The primary lytic mechanism employed by CD4+ T cells is Fas-dependent, but can be MHC-unrestricted. Thus, T cell-mediated Fas-FasL interactions could directly contribute to the pathology of EAE and MS. This review summarizes studies from our laboratory and others that implicate Fas-FasL interactions in both the pathogenesis and regulation of demyelinating diseases.
Sabelko-Downes
K A
KA
Department of Molecular Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Russell
J H
JH
Cross
A H
AH
D000818:Animals; D016923:Cell Death / Q000276:immunology; D020278:Demyelinating Autoimmune Diseases, CNS / Q000276:immunology*; D003711:Demyelinating Diseases / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D053222:Fas Ligand Protein; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008822:Mice, Transgenic; D018448:Models, Immunological; D009103:Multiple Sclerosis / Q000276:immunology; D009186:Myelin Sheath / Q000276:immunology; D009836:Oligodendroglia / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D019014:fas Receptor / Q000378:metabolism*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019014:fas Receptor