Indefinite survival of peripheral nerve allografts after temporary Cyclosporine A immunosuppression

Abstract

It is hypothesized that unlike solid organ transplants immunosuppression of peripheral nerve allografts is needed only for the finite time period required for regeneration of proximal host nerve axons through the allograft and subsequent re-establishment of host end-organ connections. The aim of this study was to explore the consequences of temporary and continuous systemic Cyclosporine A (CsA) immunosuppression upon peripheral nerve allograft survival. Buffalo rats received Lewis nerve allografts under CsA immunosuppression (5 mg/kg/day) either continuously for 20 weeks, or for only 10 weeks followed by abrupt withdrawal. At 20 weeks, the nerve segments from both groups were regrafted into naïve Buffalo or Lewis recipients without further immunosuppression. These grafts were compared with isografts, unimmuno-suppressed allografts and allografts immunosuppressed for 10 weeks in situ. By eight weeks following regrafting, the secondary Lewis recipients had rejected the temporarily immunosuppressed allografts and accepted the continuously immunosuppressed allograft, while the secondary Buffalo recipients accepted both the temporarily and continuously immunosuppressed allografts as assessed by histology and morphometry. Functional recovery was earlier in secondary recipient strain animals that received temporarily immunosuppressed allografts in comparison to those that received continuously immunosuppressed allografts. Analysis of secondary recipients of temporarily immunosuppressed allografts demonstrated greater in vitro MLR and LDA reactivity than did those receiving continuously immunosuppressed allografts. These findings support the hypothesis that donor alloantigens are lost or replaced by the recipient after immunosuppression withdrawal. Moreover, the change to recipient antigenicity in the nerve allograft is retarded and incomplete under continuous CsA immunosuppression, resulting in acceptance by both secondary donor and recipient strains upon regraftment.