Glycobiology Advance Access originally published online on February 26, 2008
Glycobiology 2008 18(5):408-413; doi:10.1093/glycob/cwn017
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Roles of complex gangliosides in the development of experimental autoimmune encephalomyelitis
2 Department of Neurology, Kinki University School of Medicine, Osaka
3 Department of Biochemistry, Nagoya University School of Medicine, Nagoya, Japan
1 To whom correspondence should be addressed: Tel: +81-72-366-0221; Fax: +81-72-368-4846; e-mail: kusunoki-tky{at}umin.ac.jp
Received on September 11, 2007; revised on December 28, 2007; accepted on February 20, 2008
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.
Key words: EAE / MS / neuroimmunology / rodent / cell surface molecules