title: Roles of complex gangliosides in the development of experimental autoimmune encephalomyelitis.
abstract: We induced experimental autoimmune encephalomyelitis (EAE) in GM2/GD2 synthase knockout mice (GM2/GD2-/-), which cannot synthesize complex gangliosides, such as GM1, GD1a, GD1b, GT1b, and GQ1b, to investigate the roles of complex gangliosides in the pathogenesis of this disease. We used myelin-oligodendrocyte glycoprotein (MOG) as an immunogen. In active immunization EAE, the severity of clinical score was not different but the disease onset was significantly delayed in GM2/GD2-/- compared with those in wild-type mice. When we transferred MOG-reactive T cells from GM2/GD2-/- or wild-type mice to wild-type mice, no significant differences were observed between the two groups. In contrast, when we transferred MOG-reactive T cells from wild-type mice to GM2/GD2-/- or to wild-type mice, the onset of EAE in GM2/GD2-/- mice was delayed. The recall response of MOG-specific T cells, the function of antigen presenting cells, or the expression of several adhesion molecules in the endothelium were not significantly different between GM2/GD2-/- and wild-type mice. On the other hand, quantitative analysis of cellular infiltration in the central nervous system (CNS) on day 9 of active immunization EAE showed that the CD4+ cell number in the CNS isolated from GM2/GD2-/- mice was significantly less than that from wild-type mice. It indicated that the delayed onset of EAE in GM2/GD2-/- mice was due to the delay of the migration of pathogenic T cells into the CNS. Thus, the complex gangliosides may be involved in the T cell-endothelial cell interaction in the pathogenetic process of EAE.
authors.affiliation: Department of Neurology, Kinki University School of Medicine, Osaka, Japan.
authors.forename: Katsuichi
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Kazuo
authors.initials: K
authors.lastname: Takada
authors.forename: Keiko
authors.initials: K
authors.lastname: Furukawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Furukawa
authors.forename: Susumu
authors.initials: S
authors.lastname: Kusunoki
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D002490:Central Nervous System / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D005732:Gangliosides / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology / Q000494:pharmacology; D063308:Myelin-Oligodendrocyte Glycoprotein
chemical_list: D015704:CD4 Antigens; D005732:Gangliosides; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein