Previous investigations have shown that cytotoxic T lymphocytes (CTLs) contribute to muscle pathology in the
dystrophin-null mutant mouse (mdx) model of
Duchenne muscular dystrophy through
perforin-dependent and
perforin-independent mechanisms. We have assessed whether the CTL-mediated pathology includes the promotion of
eosinophilia in dystrophic muscle, and thereby provides a secondary mechanism through which CTLs contribute to
muscular dystrophy. Quantitative immunohistochemistry confirmed that
eosinophilia is a component of the mdx dystrophy. In addition, electron microscopic observations show that eosinophils traverse the basement membrane of mdx muscle fibers and display sites of close apposition of eosinophil and muscle membranes. The 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
intraperitoneal 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 concentration of CTLs in dystrophic muscle, produced a significant reduction in
eosinophilia. 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.