Dominance of autoreactive T cell-mediated delayed-type hypersensitivity or antibody-mediated demyelination results in distinct forms of experimental autoimmune neuritis in the Lewis rat.
The role of anti-myelin antibodies in the pathogenesis of experimental autoimmune neuritis (EAN) induced in the Lewis rat by immunization with peripheral nerve myelin has been assessed. Passive transfer with lymph node cells (LNC) or purified serum immunoglobulin from rats with EAN was employed to directly measure the contribution of B cells and anti-myelin antibodies to demyelination and disease. Lewis rats with EAN transferred by LNC or purified serum immunoglobulin from EAN donors in conjunction with a low dose of P2-specific CD4+ T cells demonstrated profound histopathological and neurophysiological evidence of demyelination during disease. In contrast, the classical adoptive transfer model of EAN in the Lewis rat induced by the injection of P2-specific CD4+ T cells was characterized by histopathological and neurophysiological evidence of axonal dysfunction and degeneration with limited demyelination. These findings demonstrate that the synergistic action of T cells and anti-myelin antibodies mediating demyelination or purely T cell mediated axonal dysfunction and degeneration are distinct pathways by which a specific autoimmune response in the peripheral nervous system can cause neurological disease.
Taylor
J M
JM
Department of Medicine, University of Sydney, NSW, Australia.
Pollard
J D
JD
D000200:Action Potentials; D019264:Adoptive Transfer; D000818:Animals; D000906:Antibodies / Q000032:analysis / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D015551:Autoimmunity / Q000276:immunology*; D003711:Demyelinating Diseases / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D005073:Evoked Potentials, Somatosensory; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018482:Muscle, Skeletal / Q000503:physiopathology; D009186:Myelin Sheath / Q000276:immunology; D009420:Nervous System / Q000473:pathology / Q000503:physiopathology; D009443:Neuritis / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology*
D000906:Antibodies