Role of pathogenic T cells and autoantibodies in relapse and progression of myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis in LEW.1AV1 rats.
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.
Matsumoto
Yoh
Y
Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan. matyoh@tmin.ac.jp
Park
Il-Kwon
IK
Hiraki
Keiko
K
Ohtani
Shin
S
Kohyama
Kuniko
K
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D005260:Female; D007155:Immunologic Factors / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D009900:Optic Nerve / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000276:immunology / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D012008:Recurrence; D013116:Spinal Cord / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D000939:Epitopes; D007155:Immunologic Factors; C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010455:Peptides; D011948:Receptors, Antigen, T-Cell