Mechanisms of cell-mediated myocytotoxicity in the peripheral blood of patients with inflammatory myopathies.
Cell-mediated cytotoxicity is thought to play an important role in the immunopathogenesis of inflammatory myopathies. We determined whether lymphocytes circulating in patient peripheral blood contain automyocytotoxic precursors. Peripheral blood mononuclear cells, sheep red blood cell rosetting (E+) and nonrosetting (E-) cells, were isolated from patients with polymyositis or dermatomyositis and tested for their ability to kill autologous-cultured myotubes derived from diseased muscle biopsies. Patient-derived as well as normal allogeneic mononuclear cells lysed both polymyositis-dermatomyositis and nonrelated myotubes. However, whereas patient E+ cells were preferentially cytotoxic to autologous myotubes, their E-cells did not discriminate autologous from allogeneic targets. Furthermore, cultures of patient E+ cells triggered by phytohemagglutinin and interleukin-2 maintained myocytotoxic potential. In these cultures, virtually all autologous but only 50% of allogeneic killing was mediated by CD3+ T cells. Moreover, autologous cell-mediated killing was abrogated by anti-CD3 monoclonal antibodies. In conclusion, both myocytotoxic CD3+ T-cell clones specific for autologous myotubes, as well as non-T cells, which are nonspecifically myocytotoxic, are present in the peripheral blood of patients with inflammatory myopathies.
Bank
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Department of Medicine, Chaim Sheba Medical Center, Tel Hashomer, Israel. ibank@post.tau.ac.il
Miranda
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AF
Chess
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D002469:Cell Separation; D002478:Cells, Cultured; D005591:Chemical Fractionation; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D003882:Dermatomyositis / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007111:Immunity, Cellular; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D009132:Muscles / Q000166:cytology; D017285:Polymyositis / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*