Induction of neonatal immunologic tolerance to heart transplantation by intrathymic myocardial cell inoculation in rats.

To induce immunologic tolerance, intrathymic inoculation of myocardial cells in rats was performed during the neonatal period. Isolated myocardial cells from Wistar-Lewis (LEW/Crj) rat hearts were inoculated into the thymi of incompatible neonatal Wistar-King (WKAH/HKm) rats without use of immunosuppressants. Ten weeks later the heart from the LEW donor was transplanted heterotropically to the pretreated male WKAH rat (group 1, n = 14). As controls (groups 2 through 4), heart transplantation was performed in each of 10-week-old rats as follows: (1) The syngeneic heart was transplanted (group 2, n = 4); (2) the allogeneic heart was transplanted without use of immunosuppressants (group 2, n = 12); and (3) the allogeneic heart was transplanted with use of immunosuppressants (cyclosporine, 20 mg/kg/day, for 10 days after transplantation, (group 4, n = 5). In groups 1 through 3, four rats with heart transplants in each group were killed on the seventh day after transplantation and were histopathologically examined. No early rejection was seen in group 1. Hematoxylin-eosin staining of the thymus from the inoculated recipient revealed that donor myocardial cells continued to survive in the thymic tissue. The remaining rats in groups 1, 3, and 4 were saved for study of graft survival time. The longest proven graft survival in group 1 was 390 days, whereas it was only 7 days in group 3. These results indicated that intrathymic inoculation of donor myocardial cells in rats into incompatible neonatal recipients induced donor-specific tolerance for subsequent heart transplantation.