REJECTION OF SPONTANEOUSLY ACCEPTED RAT-LIVER ALLOGRAFTS WITH RECIPIENT INTERLEUKIN-2 TREATMENT OR DONOR IRRADIATION

While MHC incompatible DA (RT1(a)) to Lewis (RT1(1), LEW) rat liver al lografts are acutely rejected, the reciprocal LEW to DA liver grafts a re spontaneously accepted, The mechanism of this acceptance remains un clear, We evaluated the effect of donor treatment with total body irra diation (TBI) or gadolinium chloride (GdCl3), and recipient treatment with exogenous IL-2 after transplantation on the survival of the spont aneously accepted liver grafts, Male LEW and DA rats were used as dono rs and recipients for orthotopic liver allo- or iso-graft transplants, The LEW liver donor was treated by TBI (10 gray) 7 days before transp lantation, or LEW donor Kupffer cell phagocytosis was blocked with GdC l3 (7 mg/kg) on days -2 and -1 pretransplant. In an attempt to reverse LEW liver graft acceptance, 180,000 units human IL-2 (hIL-2) were adm inistered daily IP to the DA liver recipients from days 1 to 7 after l iver grafting, While untreated LEW recipients rejected DA liver grafts within 13 days, DA recipients accepted LEW livers indefinitely (>302 days), In contrast, irradiation of the LEW liver donor prevented the s pontaneous acceptance by DA recipients, and resulted in acute rejectio n of the liver grafts in 9-20 days, However, spontaneous graft toleran ce was restored by parking the irradiated LEW donor Liver in naive LEW rats for 48 hr before retransplantation to DA recipients (>50 days), When LEW donors were treated with GdCl3, which is known to block Kupff er cell phagocytosis and antigen processing, the spontaneous acceptanc e of the LEW liver grafts by DA recipients was unaffected, However, wh en exogenous rhIL-2 was given daily, LEW liver allografts were rejecte d by the DA recipients, The resulting liver failure correlated with a progressive increase in serum bilirubin and the development of a predo minantly lymphocytic portal tract infiltration, bile duct epithelial d amage, and portal vein endothelitis, which is consistent with acute al lograft rejection, LEW and DA recipients of liver isografts developed no toxicity and survived indefinitely (>100 days) when treated with th e same dose of IL-2, These results indicate that spontaneous rat liver allograft acceptance is associated with the presence of radiosensitiv e cells in the donor liver that may interact with recipient T cells to inhibit (Th1) production of IL-2.