Helper (CD4(+)) and cytotoxic (CD8(+))T cells promote the pathology of dystrophin-deficient muscle

Duchenne muscular dystrophy (DMD) and mdx mouse dystrophy result from mutat ions in the dystrophin gene. Although these mutations are primarily respons ible for the defects that underlie the pathology of dystrophinopathies, oth er factors may contribute importantly to the pathology. In the present inve stigation, we tested whether T cells present in mdx muscles are activated a nd contribute significantly to the pathological process. Flow cytometric an alyses showed a significantly higher frequency of activated CD44(high) T ce lls in the blood and muscle of mdx mice when compared to normal B10 mice. H owever, the frequency of activated T cells was not elevated in mdx lymph no des, suggesting muscle-specific T cell activation. In vivo antibody-mediate d depletions of CD4(+) T cells from mdx mice significantly reduced the amou nt of histologically discernible muscle pathology by 61% in mdx mice, while depletion of CD8(+) T cells resulted in a 75% decrease in pathology. Final ly, adoptive transfer of mdx immune cells in combination with muscle extrac ts resulted in muscle pathology in healthy murine recipients. These results indicate that T cells promote the mdx pathology and suggest that immune-ba sed therapies may provide benefit to DMD patients. (C) 2000 Academic Press.