Role of pathogenic T cells and autoantibodies in relapse and progression of myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis in LEW.1AV1 rats.

Abstract	Accumulating evidence suggests that T cells and autoantibodies reactive with myelin oligodendrocyte glycoprotein (MOG) play a critical role in the pathogenesis of multiple sclerosis (MS). In the present study, we have tried to elucidate the pathomechanisms of development and progression of the disease by analysing T cells and autoantibodies in MOG-induced rat experimental autoimmune encephalomyelitis (EAE), which exhibits various clinical subtypes mimicking MS. Analysis using overlapping peptides revealed that encephalitogenic epitopes resided in peptide 7 (P7, residue 91-108) and P8 (residue 103-125) of MOG. Immunization with MOGP7 and MOGP8 induced relapsing-remitting or secondary progressive EAE. T cells taken from MOG-immunized and MOGP7-immunized rats responded to MOG and MOGP7 and sera from MOG-immunized rats reacted to MOG and MOGP1. Significant epitope spreading was not observed at either T-cell or antibody levels. Interestingly, sera from MOGP7-immunized rats with clinical signs did not react to MOG and MOG peptides throughout the observation period, suggesting that disease development and relapse in MOGP7-induced EAE occur without autoantibodies. However, MOGP7 immunization with adoptive transfer of anti-MOG antibodies aggravated the clinical course of EAE only slightly. Analysis of antibodies against conformational epitope (cme) suggests that anti-MOG(cme) may play a role in the pathogenicity of anti-MOG antibodies. Collectively, these findings demonstrated that relapse of a certain type of MOG-induced EAE occurs without autoantibodies but that autoantibodies may play a role in disease progression. Relapses and the progression of MS-mimicking EAE are differently immunoregulated so immunotherapy should be designed appropriately on the basis of precise information.
Authors	Yoh Matsumoto, Il-Kwon Park, Keiko Hiraki, Shin Ohtani, Kuniko Kohyama
Journal	Immunology (Immunology) Vol. 128 Issue 1 Suppl Pg. e250-61 (Sep 2009) ISSN: 1365-2567 [Electronic] England
PMID	19175799 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antibodies, Monoclonal Autoantibodies Epitopes Immunologic Factors Mog protein, rat Myelin Proteins Myelin-Associated Glycoprotein Myelin-Oligodendrocyte Glycoprotein Peptides Receptors, Antigen, T-Cell
Topics	Adoptive Transfer Animals Antibodies, Monoclonal (immunology) Autoantibodies (immunology) Disease Progression Encephalomyelitis, Autoimmune, Experimental (immunology, pathology) Epitopes (immunology, metabolism) Female Immunologic Factors (pharmacology) Lymphocyte Activation (drug effects, immunology) Male Myelin Proteins Myelin-Associated Glycoprotein (immunology) Myelin-Oligodendrocyte Glycoprotein Optic Nerve (immunology, metabolism, pathology) Peptides (immunology, pharmacology) Rats Rats, Inbred Lew Receptors, Antigen, T-Cell (antagonists & inhibitors, immunology, metabolism) Recurrence Spinal Cord (immunology, metabolism, pathology) T-Lymphocytes (drug effects, immunology)

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