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 i n 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-m ediated disease, experimental autoimmune myasthenia gravis (EAMG), we immunized beta 2 microglobulin (beta(2)-m) gene-disrupted (beta 2 m(-/ -)) C57BL10 (B10) mice, deficient in class I gene expression and CD8() cells, and heterozygous (beta(2)-m(+/-)) B10 mice with normal expres sion of class I molecules and sufficient CD8(+) cells with Torpedo ace tylcholine receptor in CFA, and assessed them for clinical and immunop athologic manifestations of EAMG. Despite MHC class I and CD8(+) cell deficiency, beta(2)-m(-/-) mice developed EAMG. Moreover, the incidenc e of EAMG in the beta(2)-m(-/-) mice was higher than that of beta(2)-m (+/-) heterozygous mice with normal class I expression and frequency o f 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.