Experimental Research Of Immunologic Tolerance Following Mouse Peripheral Nerve Xenotransplantation In Rats

Xenotransplantation offers a potentially unlimited source for tissues and organs for transplantation,but the strong xenoimmune responses pose a major obstacle to its application in the clinic.In this study,we investigate the rejection of mouse peripheral nerve xenografts in rats.Severe intragraft mononuclear cell infiltration,and graft distension and necrosis were detected in the recipients as early as 2 weeks after mouse nerve xenotransplantation.The number of axons in xenografts reduced progressively and became almost undetectable at week 8. However,mouse nerve xenotransplantation only led to a transient and moderate increase in the production of Th1 cytokines,including IL-2,IFN-γand TNF-α. The data implicate that cellular immune responses play a critical role in nerve xenograft rejection,but that further identification of the major effector cells mediating the rejection is required for developing effective means to prevent peripheral nerve xenograft rejection.Objective To investigate the alteration of the immunological cytokine level and histological changes of nerves.To investigate the anti-rejection effect of T cell vaccination combined with FK506 of heterogenic transplantation on rat nerve.Methods The change of nerves in general,using microscopy and electron microscope and the concentration of serum IL-2,IL-4,IFN-γ,TNF-αwere observed after 4,8 and 12weeks of transplantation,respectively.SD rats were vaccinated by the spleen cells of BABL/c mice;T cell vaccines were activated and vaccinated in the spleen cells of these SD rats.The SD rats of nerve transplantation recipient were vaccinated with T cells combined with FK506. The mixture lymphocytes culture,microcytotoxicity assay,histological alteration of nerves,humid weights of tibial anterior muscle were observed to confirm the anti-rejection effect of T cell vaccination combined with FK506 treatment.Results Inflammatory cells infiltrated after 4 weeks of transplantation, the myelin sheath structure could be seen after 4 weeks and disaggregated in 8 weeks;the concentrations of Th1 cytokine increased and Th2 decreased after 4 weeks,which statistically different from those in control group(P＜0.05).The humid weights of tibial anterior muscle of the vaccinated rats combined with FK506 treatment were statistically different from those in control group (P＜0.05),and so as the index of rejection(e.g.lymphocytes transformation efficiency)(P＜0.05).Conclusion The immunological rejection after heterogenic transplantation was mainly mediated by cellular immunity,and the level of cytokines and histological changes were most significant.T cell vaccination combined with FK506 treatment can inhibit the rejection of heterogenic transplantation on rat peripheral nerve.