Mechanisms underlying continued survival of rat kidney allografts after a short period of chemical immunosuppression.
Experiments have been carried out to investigate whether the continued survival of rat kidney allografts induced by two different methods-namely, immunological enhancement or a limited course of drug treatment with cyclosporine or cyclophosphamide, is maintained by similar mechanisms. (AS X AUG)F1 or AUG strain kidneys were transplanted to AS recipients that were treated for 14 days with cyclosporine or cyclophosphamide. The limited course of drug treatments induced indefinitely prolonged, or very extended, allograft survival. Long-surviving F1 kidney grafts were retransplanted into naive AS recipients, and by functioning for more than 100 days proved, like enhanced grafts, to be less immunogenic than normal (AS X AUG)F1 kidneys. Very prolonged survival of homozygous, incompatible AUG kidneys was only observed after the cyclosporine drug regimen-and when these grafts were retransplanted to naive second AS recipients, acute or chronic rejection ensued. However, the rejection was prevented if spleen cells from the first AS recipient were adoptively transferred to the second AS recipient at the time of retransplantation. It was concluded that suppressor cells must be present in the transferred spleen cell populations. The experiments show that, as in the case of immunological enhancement, very prolonged allograft survival brought about by a short course of immunosuppressive drug treatment is accompanied by reduction in graft immunogenicity, and by the induction of suppressor cells.