Dominance of autoreactive T cell-mediated delayed-type hypersensitivity orantibody-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 auto immune neuritis (EAN) induced in the Lewis rat by immunization with periphe ral nerve myelin has been assessed. Passive transfer with lymph node cells (LNC) or purified serum immunoglobulin from rats with EAN was employed to d irectly measure the contribution of B cells and anti-myelin antibodies to d emyelination and disease. Lewis rats with EAN transferred by LNC or purifie d serum immunoglobulin from EAN donors in conjunction with a low dose of P2 -specific CD4(+) T cells demonstrated profound histopathological and neurop hysiological evidence of demyelination during disease. In contrast, the cla ssical adoptive transfer model of EAN in the Lewis rat induced by the injec tion of P2-specific CD4(+) T cells was characterized by histopathological a nd neurophysiological evidence of axonal dysfunction and degeneration with limited demyelination. These findings demonstrate that the synergistic acti on of T cells and anti-myelin antibodies mediating demyelination or purely T cell mediated axonal dysfunction and degeneration are distinct pathways b y which a specific autoimmune response in the peripheral nervous system can cause neurological disease.