Effect of MHC class I and CD8 cell deficiency on experimental autoimmune myasthenia gravis pathogenesis

MHC class I and CD8⁺ cell deficiency have either prevented systemic lupus erythematosus-like disease in mice or enhanced type I diabetes in nonobese diabetic mice. To study the involvement of MHC class I and class I-restricted CD8⁺ T cells in the induction of a classical Ab-mediated disease, experimental autoimmune myasthenia gravis (EAMG), we immunized β2 microglobulin (β₂-m) gene-disrupted (β2 m(-/-)) C57BL10 (B10) mice, deficient in class I gene expression and CD8⁺ cells, and heterozygous (β₂- m(+/-)) B10 mice with normal expression of class I molecules and sufficient CD8⁺ cells with Torpedo acetylcholine receptor in CFA, and assessed them for clinical and immunopathologic manifestations of EAMG. Despite MHC class I and CD8⁺ cell deficiency, β₂-m(-/-) mice developed EAMG. Moreover, the incidence of EAMG in the β₂-m(-/-) mice was higher than that of β₂-m(+/- ) heterozygous mice with normal class I expression and frequency of CD8⁺ cells. The finding provided direct genetic evidence against a pathogenic effector role in C57BL10 mice for MHC class I molecule and class I-restricted CD8⁺ T cells in EAMG pathogenesis.