Immunologic mechanism following liver transplantation. An experimental study in the rat

: To investigate the immunological status of hepatic grafts we transplanted livers from different inbred rats orthotopically on 58 LEW rats; rearterialization of the grafts was achieved with an hepatico aortal segment of the donor. Survival time depended on the donor strain; LBNF1-allografts survived in 67% (n = 12), WiS- in 60% (n = 20) and BUF- in 43% (n = 14) indefinitely. In the DA-to-LEW-combination we found no long-term survivor. Liver perfusates (LP) were prepared from 10 BDE and 10 LEW; after keeping the livers for 6 h at room temperature we perfused via portal vein with 2 ml/g Ringer's solution five times. The treatment of BDE-kidney recipients (LEW) with LP showed prolonged survival; at 5 days application 10.2 +/- 1.3 d (control: 6.5 +/- 0.5 d; P less than 0.001), at 10 days treatment 15.3 +/- 7.3 d. In vitro LP inhibited the PHA-stimulation of LEW lymphoid cells in more than 90% and the ConA-stimulation of LEW spleen cells in more than 95%. In MLC LP showed strong inhibitory effect (inhibition rate greater than 97%) even when different combinations of responding and stimulating cells were used. We assume that an unspecific immunosuppressive hepatic factor is released from ischemic damaged liver grafts which is able to prevent rejection in the induction phase. In WiS-liver recipients surviving for more than 4 months GvHR was tested after splenectomy with spleen cells. All tests showed a grade III reaction. Donor-specific skin grafts which were transplanted on these recipients survived indefinitely while third party skin grafts were regularly rejected (7.6 +/- 0.5 d). We therefore can conclude that the cellular immunosurveillance is intact, but the immunological response against donor-specific antigens is reduced. With transfer of serum from long-term-surviving WiS-liver recipients (greater than 6 months) WiS-kidney grafted LEW were able to survive also prolonged (20.7 +/- 3.4 d, control 6.2 +/- 1.0 d; P less than 0.001). Lymphoid cell transfer (1 X 10(8)) did did not result in significant prolongation of survival time (8.0 +/- 2.0 d). These observations suggest that in the steady phase specific humoral transfer factors are responsible for prolonged survival of hepatic grafts.