Experimental study on peripheral nerve xenograft by induction of immuno-tolerance

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Anti-CD4 treatment has been shown to prolong survival of skin allografts as well as cardiac allografts. Anti-CD4 and anti-CD8 monoclonal antibodies prolonged concordant rat-to-mouse cardiac xenograft survival The fusion protein, CTLA4Ig, blocks T-cell-dependent antibody production and inhibits the proliferation of activated T cells restimulated with allogeneic cell linesWe transplanted Lewis rat sural nerve of 10mm length to the defect of mouse (BALB/c) sciatic nerve of 3mm using microsurgical technique under operating microscope. The experimental animals were divided into the following three groups : Group 1 (control) ; no treatment, Group 2 ; anti-CD4 (125/μg mouse) was given intraperitoneally on 2 days and immediately before transplantaticn, Group a CTLA4Ig (25μg/mouse) was given intraperitoneally just after transplantaticn and on 1 day and 3 days after transplantation. We examined the motor function recovery by Waking tract analysis and the specimen of the grafted nerve was taken at 8 weeks after transplantation for histological examinationThe walking tract test showed no evident differences in recovery of hindlimb motor function for 8 weeks after transplantation between three groups. The histological examination revealed the following results : In Group 1, there was remarkable formation of collagen fibers and the regenerated myelinated axons were only scattered in the xenograft and the diameter of the axon was small and the myelin sheath was thin. In Group 2, 3, on the contrary, many myelinated axons were observed diffusely in the grafted nerve. And the diameter of the regenerated axons was larger and the myelin sheath was thicker than Group 1From this study we conclude that short-term and small amount of administration of anti-CD4 or CTLA4Ig enables the axonal regeneration through peripheral nerve xenograft between rat and mouse