Indefinite survival of peripheral nerve allografts after temporary Cyclosporine A immunosuppression

It is hypothesized that unlike solid organ transplants immunosuppression of peripheral nerve allografts is needed only for the finite time period requ ired for regeneration of proximal host nerve axons through the allograft an d subsequent re-establishment of host end-organ connections. The aim of thi s study was to explore the consequences of temporary and continuous systemi c Cyclosporine A (CsA) immunosuppression upon peripheral nerve allograft su rvival. Buffalo rats received Lewis nerve allografts under CsA immunosuppre ssion (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 gr oups were regrafted into naive Buffalo or Lewis recipients without further immunosuppression. These grafts were compared with isografts, unimmunosuppr essed allografts and allografts immunosuppressed for 10 weeks in situ. By e ight weeks following regrafting, the secondary Lewis recipients had rejecte d the temporarily immunosuppressed allografts and accepted the continuously immunosuppressed allograft, while:the secondary Buffalo recipients accepte d both the temporarily and continuously immunosuppressed allografts as asse ssed by histology and morphometry. Functional recovery was earlier in secon dary recipient strain animals that received temporarily immunosuppressed al lografts in comparison to those that received continuously immunosuppressed allografts. Analysis of secondary recipients of temporarily immunosuppress ed allografts demonstrated greater in vitro MLR and LDA reactivity than did those receiving continuously immunosuppressed allografts. These findings s upport the hypothesis that donor alloantigens are lost or replaced by the r ecipient after immunosuppression withdrawal. Moreover, the change to recipi ent antigenicity in the nerve allograft is retarded and incomplete under co ntinuous CsA immunosuppression, resulting in acceptance by both secondary d onor and recipient: strains upon regraftment.