Induction of immune tolerance in adult rabbits undergoing heterotopic cardiac transplantation.

OBJECTIVE

To induce experimental immune tolerance in rabbits and observe its effects on heterotopic cardiac transplantation.

METHODS

Donor's splenic lymphocytes pretreated with platinum metal chelator were injected into the recipient's mesenteric-portal vein. Cyclosporin A was perfused through the donor's heart.

RESULTS

The injection of donor's splenic lymphocytes before transplantation could significantly prolong the survival time of the heterotopically transplanted heart. The effect of two injections was better than that of one. Radioactive tracer studies showed that the 99mTc-HMPAO tagged lymphocytes injected into the recipient rabbit were later concentrated in the liver, though initially they were distributed in multiple organs. The induced immune tolerance was antigen-specific, and it neither affect the other immune functions of the lymphatic system prominently nor exert any harmful effect on the recipient's liver and renal functions. The perfusion of cyclosporin A through the donor heart could block the glycosyl groups, such as D-glucose, D-mannose or N-acetyl-galactosamine on the surface of the myocardial cells, thus might change the antigenic expression, effectively preventing rejection of the graft by the host, and might be considered as a new method to block graft rejection in cardiac transplantation. The combined use of the above-mentioned two methods acted on both the host and the donor, thus reducing the exposed antigens on the donor organ as well as the immune reaction against the donor antigens, and resulting in synergistic effect in inducing immune tolerance in adult rabbits, and resulting in relatively long-term survival of transplanted hearts.

CONCLUSION

This report may provide the experimental basis for inducing immune tolerance in clinical transplantation.