title: Necrosis, sarcolemmal damage and apoptotic events in myofibers rejected by CD8+ lymphocytes: Observations in nonhuman primates.
abstract: To detect the mechanisms of death in allogeneic myofibers rejected by the immune system, myoblasts were allotransplanted in muscles of macaques immunosuppressed with tacrolimus. Immunosuppression was stopped 1month later to induce a massive rejection of allogeneic myofibers. Grafted sites were biopsied at 2-week intervals and analyzed by histology. The loss of allogeneic myofibers was rapid and concomitant with an intense infiltration of CD8+ lymphocytes. Several necrotic myofibers were observed in the lymphocyte accumulations by intracellular complement immunodetection. Dystrophin and spectrin immunodetection showed sarcolemmal damage in myofibers surrounded and invaded by CD8+ lymphocytes. Active caspase-3 was immunodetected in some myofibers surrounded by CD8+ lymphocytes. This is the first evidence that the collapse of myofibers attacked by T lymphocytes occurs by necrosis possibly due to damage of the sarcolemma. Caspase 3 is activated at least in some myofibers, but there was no evidence of a complete classical process of apoptosis.
authors: Neurosciences Division - Human Genetics, CHUQ Research Center - CHUL, Quebec, QC, Canada. Daniel.Skuk@fmed.ulaval.ca
authors: Daniel
authors: D
authors: Skuk
authors: Jacques P
authors: JP
authors: Tremblay
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D053148:Caspase 3 / Q000096:biosynthesis; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008251:Macaca; D018482:Muscle, Skeletal / Q000276:immunology / Q000637:transplantation; D009336:Necrosis / Q000276:immunology; D012508:Sarcolemma / Q000276:immunology* / Q000473:pathology; D016559:Tacrolimus / Q000494:pharmacology
chemical_list: D007166:Immunosuppressive Agents; D053148:Caspase 3; D016559:Tacrolimus