EFFECT OF 15-DEOXYSPERGUALLIN ON ACCELERATED REJECTION IN RAT-HEART TRANSPLANTATION

The effect of 15-deoxyspergualin (DSG) on accelerated rejection was evaluated using a rat heart transplantation model. Lewis rats (LEW, RT1(1)) served as the organ recipient and Brown Norway rats (BN, RT1(n)) as the donor. In the accelerated rejection model, the LEW recipient was sensitized with BN skin and BN heart was transplanted 7 days later; the heart graft was rejected within 2 days (n = 7). Histologically, the graft showed coagulation necrosis and hemorrhage throughout the myocardium. DSG (2.5 mg/kg/day) was administered to the recipient under the following three protocols: group 1: during the sensitization period (7 days); group 2: from 3 days after the sensitization to 2 days after grafting (7 days), and group 3: immediately after heart transplantation. The mean graft survival period in groups 1,2, and 3 was 4.3 +/- 0.8 days (n = 7, p < 0.01, vs. untreated host), 11.7 +/- 2.1 days(n = 7, p < 0.001, vs. untreated host), and 2.0 +/- 0 days (n = 6), respectively. The rejected grafts in groups 1 and 3 histologically showed coagulation necrosis and hemorrhage. By contrast, in group 2, the major histological change was interstitial lymphocyte infiltration and there were few findings such as coagulation necrosis or hemorrhage. In the complement-dependent cytotoxicity test, serum obtained at the second posttransplant day from the recipients treated in group 1 showed a high cytotoxicity level, although the cytotoxicity level of serum obtained from the recipients treated in group 2 was consistently low. Flow cytometric study revealed that DSG could suppress the proliferation of OX3- and OX33-positive cells if the recipients were treated in group 2. In conclusion, the heart graft survival period was markedly prolonged and the humoral reaction was suppressed by maintaining the recipient serum cytotoxicity level low only when DSG was administered both during the sensitization period and after heart grafting.