Helper (CD4+) and Cytotoxic (CD8+) T Cells Promote the Pathology of Dystrophin-Deficient Muscle

Duchenne muscular dystrophy (DMD) and mdx mouse dystrophy result from mutations in the dystrophin gene. Although these mutations are primarily responsible for the defects that underlie the pathology of dystrophinopathies, other factors may contribute importantly to the pathology. In the present investigation, we tested whether T cells present in mdx muscles are activated and contribute significantly to the pathological process. Flow cytometric analyses showed a significantly higher frequency of activated CD44high T cells in the blood and muscle of mdx mice when compared to normal B10 mice. However, the frequency of activated T cells was not elevated in mdx lymph nodes, suggesting muscle-specific T cell activation. In vivo antibody-mediated depletions of CD4+ T cells from mdx mice significantly reduced the amount of histologically discernible muscle pathology by 61% in mdx mice, while depletion of CD8+ T cells resulted in a 75% decrease in pathology. Finally, adoptive transfer of mdx immune cells in combination with muscle extracts resulted in muscle pathology in healthy murine recipients. These results indicate that T cells promote the mdx pathology and suggest that immune-based therapies may provide benefit to DMD patients.