Eosinophilia of dystrophin-deficient muscle is promoted by perforin-mediated cytotoxicity by T cell effectors

Previous investigations have shown that cytotoxic T lymphocytes (CTLs) cont ribute to muscle pathology in the dystrophin-null mutant mouse (mdx) model of Duchenne muscular dystrophy through perforin-dependent and perforin-inde pendent mechanisms. We have assessed whether the CTL-mediated pathology inc ludes the promotion of eosinophilia in dystrophic muscle, and thereby provi des a secondary mechanism through which CTLs contribute to muscular dystrop hy. Quantitative immunohistochemistry confirmed that eosinophilia is a comp onent of the mdx dystrophy. In addition, electron microscopic observations show that eosinophils traverse the basement membrane of mdx muscle fibers a nd display sites of close apposition of eosinophil and muscle membranes. Th e close membrane apposition is characterized by impingement of eosinophilic rods of major basic protein into the muscle cell membrane. Transfer of mdx splenocytes and mdx muscle extracts to irradiated C57 mice by intraperiton eal injection resulted in muscle eosinophilia in the recipient mice. Double -mutant mice lacking dystrophin and perforin showed less eosinophilia than was displayed by mdx mice that expressed perforin. Finally, administration of prednisolone, which has been shown previously to reduce the concentratio n of CTLs in dystrophic muscle, produced a significant reduction in eosinop hilia. These findings indicate that eosinophilia is a component of the mdx pathology that is promoted by perforin-dependent cytotoxicity of effector T cells, However, some eosinophilia of mdx muscle is independent of perforin -mediated processes.