Acute rejection of myofibers in nonhuman primates: key histopathologic features

The aim of this study was to define the histologic features of acute rejection of myofibers, particularly in the context of therapeutic myogenic cell transplantation. Myoblasts expressing or not expressing β-galactosidase were transplanted into 13 macaques that were divided into 3 protocols: withdrawal of immunosuppression, low immunosuppression, and progressive reduction of immunosuppression. The biopsy samples were obtained from cell-grafted sites at different intervals, and cryostat sections of biopsies were analyzed. The grafts were lost in all the monkeys at different periods after transplantation depending on the protocol and in association with low blood levels of tacrolimus. In all cases, graft loss was associated with the presence of dense focal accumulations of CD8-positive and CD4-positive lymphocytes and a component of macrophages. The lymphocyte accumulations totally or partially surrounded some myofibers and often invaded them; they were mainly endomysial. These histopathologic patterns in nonhuman primates and their similarity with preliminary observations in humans may facilitate the translation of these results to the histologic diagnosis of acute rejection of myofibers in human clinical trials of myogenic cell transplantation and probably gene therapy.