Although nervous tissue allografts survive during treatment with the immunosuppressive agent Cyclosporin-A (Cy-A), they are rejected once therapy is stopped. Accordingly, we have begun to explore ways in which the antigenicity of the allograft might be eliminated or the host rendered tolerant to the antigens of the allograft. In one study donor rats were perfused with a physiological salt solution to remove blood from their nerves prior to transplantation. Since blood alone can evoke an immune reaction, this manipulation was expected to alter allograft antigenicity. However, despite removing the blood, the nerve allografts were rejected. The perfusion procedure did not alter the viability of the grafts since they survived and underwent Wallerian degeneration in genetically compatible (i.e., isogeneic) hosts. In another study, nerve allografts, resident for 3-5 months in immunosuppressed rats, were retransplanted into non-immunosuppressed hosts. These retransplanted nerves were also rejected indicating again that allogeneic blood alone is not responsible for inciting rejection and that nerve allograft cells retain their antigenicity, even after prolonged periods of transplantation. In an attempt to induce tolerance to allograft antigens, host rats were given donor blood intravenously, at the time of nervous tissue grafting, and maintained on Cy-A for only one week. Interestingly, allogeneic neurons survived after three months whereas nerve allografts were rejected. We plan to investigate the reason for these divergent results as well as to improve upon our use of blood and Cy-A as a tolerogenic protocol. Data from other studies indicated that hamster neurons survived in the spinal cord of Cy-A immunosuppressed rats. If this result applies to other species, it suggests that xenogeneic neurons can be used clinically.
