DELETION OF SPONTANEOUS RAT-LIVER ALLOGRAFT ACCEPTANCE BY DONOR IRRADIATION

Liver transplants in rodents or pigs are often spontaneously accepted across a complete MHC mismatch. They induce tolerance to grafts of oth er organs or skin of liver donor strain and can even suppress ongoing rejection of heart grafts. It has not been established whether liver-i nduced tolerance is due to components of the liver or to passenger leu kocytes within the liver. We depleted populations of passenger leukocy tes from the transplanted liver by irradiation of tire donor with 10 G y, followed after 7 days by transplantation of the liver. Recipients o f livers from irradiated donors had a median survival of 16 days compa red with >100 days for recipients of livers from normal donors. Examin ation of recipients of irradiated donor livers showed that allograft r ejection was the cause of death. Syngeneic transplants of irradiated P VG donor to PVG recipient or of irradiated DA donor to DA recipient su rvived indefinitely. Parking of livers from irradiated PVG donors in n ormal PVG animals for 36 hr reconstituted tolerance when the livers we re retransplanted to DA recipients. Livers from irradiated donors had greatly reduced passenger leukocyte numbers compared with normal or pa rked livers, with virtually complete loss of lymphocytes. These result s show that spontaneous liver allograft acceptance is associated with populations of passenger leukocytes that are depleted by donor irradia tion.