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 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 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, beta 2-m-/- mice developed EAMG. Moreover, the incidence 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 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.
Shenoy
M
M
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston 77555.
Kaul
R
R
Goluszko
E
E
David
C
C
Christadoss
P
P
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D009157:Myasthenia Gravis / Q000276:immunology*; D011976:Receptors, Muscarinic / Q000276:immunology; D001613:beta 2-Microglobulin / Q000276:immunology
D015395:Histocompatibility Antigens Class I; D011976:Receptors, Muscarinic; D001613:beta 2-Microglobulin