Anti-CD40 ligand antibody permits regeneration through peripheral nerve allografts in a nonhuman primate model.

摘要: Systemic immunosuppression is typically required to prevent allograft rejection. Antibody-based therapies that induce immune unresponsiveness represent an appealing alternative nonspecific immunosuppression, which often associated with significant morbidity. In mice, successful prevention of nerve rejection has been demonstrated through interference the CD40/CD40 ligand interaction. This study investigated effectiveness anti-CD40 monoclonal antibody as single-agent therapy in preventing and supporting regeneration across long allografts nonhuman primates. Twelve outbred cynomolgus macaques were arranged into six genetically mismatched pairs, each animal receiving a 5-cm ulnar right arm autograft left arm. Mixed lymphocyte reaction assays used assess resulting unresponsiveness. Treated animals (n = 10) received 10 mg/kg one time, locally applied, 20 systemically on postoperative days 0, 1, 3, 10, 18, 28, then monthly. Untreated 2) served untreated controls. At 4 or 6 months after transplantation, nerves harvested for histological analysis. Four treated underwent additional challenge cessation graft harvests. Autogenous allogeneic skin inlay grafting was performed permanence induced by antibody. Animals robust allografts, similar seen control contralateral The histomorphometric analysis significantly worse measurements compared their matched concomitant had virtually no evidence allografts. Allogeneic applied 2 12 withdrawal consistently rejected. demonstrates prevents allows peripheral effect appears be transient, however, restoration immunocompetence shortly therapy.