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.