title: Chemotaxis and Immunoregulatory Function of Cardiac γδ T Cells in Dystrophin-Deficient Mice.
abstract: 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 γδ 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 γδ T cells to the cardiac muscle of mdx mice and to characterize their phenotype and functional activity. We observed no migration of γδ 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 Vγ1+/CD27+and thus produce high levels of IFN-γ. In vivo depletion of the γδ T cells revealed γδ 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 Γδ 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 γδ 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.
authors.affiliation: Laboratório de Inovações em Terapias, Ensino e Bioprodutos, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, RJ 21040-900, Brazil; cynthiac@ioc.fiocruz.br.
authors.forename: Cynthia Machado
authors.initials: CM
authors.lastname: Cascabulho
authors.affiliation: Laboratório de Inovações em Terapias, Ensino e Bioprodutos, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, RJ 21040-900, Brazil.
authors.forename: Daniela Gois
authors.initials: DG
authors.lastname: Beghini
authors.affiliation: Departamento de Anatomia Patológica e Citopatologia, Instituto Fernandes Figueira, FIOCRUZ, Rio de Janeiro, 22250-020, Brazil; and.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Meuser-Batista
authors.affiliation: Departamento de Farmacologia, Instituto de Tecnologia em Fármacos Far-Manguinhos and Centro de Desenvolvimento Tecnológico em Saúde, FIOCRUZ, Rio de Janeiro, 21041-250, Brazil.
authors.forename: Carmen
authors.initials: C
authors.lastname: Penido
authors.affiliation: Laboratório de Inovações em Terapias, Ensino e Bioprodutos, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, RJ 21040-900, Brazil.
authors.forename: Andrea
authors.initials: A
authors.lastname: Henriques-Pons
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000235:genetics / Q000276:immunology*; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D016189:Dystrophin / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018345:Mice, Knockout; D020388:Muscular Dystrophy, Duchenne / Q000276:immunology*; D009206:Myocardium / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D018932:Chemokine CCL2; D018946:Chemokine CCL5; D016189:Dystrophin; D016692:Receptors, Antigen, T-Cell, gamma-delta