Peripheral Nerve Allograft Transplantation with FK506

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Abstract
Two-centimeter nerve allografts were transplanted across a major histocompatibility barrier from donor ACI rats into a 0.5-cm gap in the sciatic nerve of recipient Lewis rats and immunosuppressed with FK506, 2 mg/kg per day for 3 months. One group of animals continued to receive intermittent immunosuppression with FK506, 2 mg/kg twice a week for another 2 months, whereas the second group of animals received no further immunosuppression in order to determine whether rejection of nerve allografts can still occur after immunosuppression is withdrawn, even after the axons have regenerated through the nerve graft. The sciatic function index improved from −76.3 at 3 months to −46.6 at 5 months in those animals continuing to receive intermittent immunosuppression, but only improved to −66.8 at 5 months when immunosuppression was discontinued. Similarly, somatosensory evoked potentials demonstrated an improvement in relative latency from 2.3 msec at 3 months to 0.34 msec at 5 months in animals continuing to receive intermittent immunosuppression, but only improved to 1.29 msec at 5 months when immunosuppression was discontinued. Nerve allografts continuing to receive intermittent immunosuppression showed no signs of rejection by light or electron microscopy and no significant difference compared with isografts, whereas nerve allografts whose immunosuppression had been stopped at 3 months showed mild signs of rejection, less regeneration, and a smaller number of nerve fibers. Immunohistology revealed only a small number of Lewis-derived Schwann's cells in the ACI nerve allografts in animals continuing to receive intermittent immunosuppression, but an increasing number of Lewis-derived Schwann's cells in animals whose immunosuppression was discontinued. Therefore, this study demonstrates that rejection of nerve allografts can be successfully prevented by immunosuppression using FK506 with the Schwann's cells remaining donor derived. However, if immunosuppression is withdrawn even after the axons regenerate across the distal nerve juncture, an ongoing rejection process still occurs, which can be confirmed both histologically and by functional testing, and the Schwann's cells then become recipient derived (Lewis).

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