Immunomodulation with anti-αβ T-cell receptor monoclonal antibodies in combination with cyclosporine a improves regeneration in nerve allografts

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To investigate the use of nerve allografts in animals treated with a short-term combined protocol of anti-alpha/beta T-cell receptor monoclonal antibodies and Cyclosporine A (CsA) to induce tolerance and allow for nerve regeneration. An established rat sciatic nerve model was used. A total of 76 rats were used in this experiment (Lew RT1L n=44, Lewis-Brown-Norway (LBN RT1L+N, n=22), Brown-Norway (BN RT1N, n=10). Sciatic nerve (1.5 cm) deficits were created in the Lewis rats and the animals were randomized to seven treatment groups to allow for repair with isograft controls (LEW-LEW) and with both semiallogeneic (LBN-LEW) and full major histocompatability (MHC) mismatched (BN-Lew) allografts. Nerve regeneration was evaluated at 6 and 12 weeks by somatosensory evoked potentials (SSEP) and standardized pin-prick and toe-spread tests. Nerve samples were harvested at 12 weeks and stained with toluidine blue to assess the total number of myelinated axons, axon area, and myelin sheath thickness. Muscle denervation atrophy was evaluated by gastrocnemius weights. Immunocompetence was investigated through skin grafting and fluorescent activated cell sorting (FACS) analysis. Improved functional, electrophysiologic, and histomorphometric outcomes were observed in animals treated with anti-alpha/betaTCR mAbs and CsA after nerve allograft transplantation when compared to animals receiving no treatment and CsA alone. The immunomodulating protocol of combination anti-alpha/beta TCR mAbs and CsA for a 5 week period altered the rejection process, affording nerve regeneration. It may provide for an expanded source of nerve tissue to alleviate the morbidity of harvesting peripheral nerves from multiple sites for those afflicted with extensive peripheral nerve injuries.