| Co-Investigator(Kenkyū-buntansha) |
ONODERA Hiroshi Tohoku University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (20214207)
FUJIHARA Kazuo Tohoku University, Hospital, Associate Professor, 医学部附属病院, 助教授 (70280873)
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| Research Abstract |
We analyzed the molecular immunopathogeneses of optic-spinal multiple sclerosis (OSMS) relatively common in Japan and conventional MS (CMS) commonly seen in Western countries. 1) We applied the sensitive isoelectric focusing method to detect OB and found that the frequencies of OB were 67.9% in CMS and 10% in OSMS. 2) We studied clonally expanded T cells during relapse with the CDR3 spectratyping. Vβ5.2 was frequently expanded in both CSF and blood. However, there was no OSMS-specific Vβ expansion. Identical amonoacid sequences in CDR3 were detected in cases with Vβ5.2 expansion, suggesting the pathogenetic association. 3) The immunohistochemical analyses of chemokines and the receptors in MS brains showed that CMS was a Th1-dominant condition. In contrast, the CCR5/CCR3 ratio in the CSF CD4+cells was significantly lower in OSMS than in CMS. 4) NKT cells probably suppress MS, but these lymphocytes failed to proliferate in the presence of α-GalCer, a ligand of CD1d of NKT cells, in some patients. 5) CCR7+cells, which play a pivotal role in antigen presentation and immunological memory, were seen in the region adjacent to the plaques, and SLC, a CCR7 ligand, was expressed in the vascular endothelial cells. These molecules may be involved in the migration of leukocytes to the lesions. 6) We studied the CSF IgG epitopes with the phage display method. Common aminoacid sequences were detected in each case, and they were frequently homogenous to herpes viral proteins. However, those sequences in each patient were unique. The absorption of CSF IgG reacted to the sequences presented by the phages did not change the banding pattern of OB. Therefore, each band of OB probably consists of multiple antibodies. Our study demonstrated that OSMS was distinct from CMS in OB and Th1 responses. We also characterized the lymphocytes and the peptides reacting to CSF IgG in CMS.
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