Although clinical advances in reconstruction strategies have continued to evolve over the years, there continues to be a limitation in functional reconstitution for patients afflicted with traumatic injuries. Both iatrogenic or traumatic peripheral nerve injuries, which result in significant morbidity for patients, often require interposition nerve autografts [1]. However, nerve autografts do have acknowledged limitation including donor availability, potential donor site morbidity including scarring, sensory loss, and painful neuroma formation [2]. Furthermore, there can be inconsistent and suboptimal outcomes for patients with autograft repairs. This led to the development of nerve allograft transplantation models under the guidance of Dr. Maria Siemionow at the Cleveland Clinic Foundation. This alternative model approach using nerve allografts does have potential drawbacks including viral transmission and the need for transient host immunosuppressive therapy. Allografts do offer the possibility to serve as a scaffold across which recipient native nerve may regenerate [3]. The development of an effective immunomodulating regimen was central to our strategy in allograft transplantation modeling. It was hoped that the immunomodulating regimen would be required only until the regeneration was complete to prevent the sequelae of immunosuppression including late opportunistic infections and malignancy. Therefore, we pursued a model that will be described within this chapter including experimental results and a current review of select allograft models that have been pursued at other institutions.

We investigated a short term combined protocol of anti-αβ T-cell receptor monoclonal antibodies (anti-αβ TCR mAbs) and cyclosporine (CsA) to induce tolerance and allow for regeneration. The rationale for this protocol was based on prior work in the laboratory demonstrating that a 5 week protocol of anti-αβ TCR mAbs in combination with CsA could be successfully used to induce tolerance in rat hind limb allograft transplantation across major histocompatibility barriers [4]. It was hypothesized that specific targeting of T cells with anti-αβ TCR mAbs in combination with CsA, which curbs nonspecific cell-mediated rejection via inhibition of the IL-2 receptor, would modulate the nerve allograft response to prevent rejection and afford successful nerve regeneration [5].