Chemotaxis and Immunoregulatory Function of Cardiac {gamma}{delta} T Cells in Dystrophin-Deficient Mice [IMMUNE REGULATION]

Duchenne muscular dystrophy (DMD) is a fatal X-linked disorder caused by mutations in the dystrophin gene that lead to degeneration of skeletal and cardiac muscles and to chronic inflammation. Despite the importance of T cells in many diseases, this cellular subpopulation has not been described in DMD patients or in mdx mice, a widely used mouse model for studying DMD. Therefore, in this study, we aimed to evaluate the migration of T cells to the cardiac muscle of mdx mice and to characterize their phenotype and functional activity. We observed no migration of T cells to skeletal muscles, but these cells were found in the hearts of mdx mice during the study period, reaching a peak in 12-wk-old mice. These cells migrate primarily owing to CCL2 and CCL5 chemokines produced by cardiac tissue, and they are V1⁺/CD27⁺ and thus produce high levels of IFN-. In vivo depletion of the T cells revealed T cell–dependent cardiac inflammatory immunoregulation, with increased numbers of CD3⁺CD4⁺, CD3⁺CD8⁺, and, in particular, F4/80⁺ cells in the heart and increased cardiac damage in mdx mice. We also observed in vitro that purified cardiac T cells are cytotoxic against adherent endomysial cardiac cells, mostly macrophages, but not against peritoneal cells, in a perforin/granzyme–dependent manner. Our present data indicate that T cells exert protective effects on the hearts of mdx mice, possibly by selectively killing pathogenic macrophages, and this function may be important for the late onset of cardiac damage in DMD.

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