SPONTANEOUS ACCEPTANCE OF LIVER ALLOGRAFTS IN THE RAT - ANALYSIS OF THE IMMUNE-RESPONSE

In a model of arterialized rat liver transplantation, the biological indicators of liver dysfunction and the phenotype and in vitro function of graft-infiltrating cells have been compared in rejected (DA-to-Lew) and spontaneously accepted (Lew-to-DA) grafts, 2-8 days after grafting. Recipients of rejected and nonrejected allografts had, during this time, similar loss in body weight and plasma levels of transaminase. The markers of cholestasis, however, increased from days 3 and 4 onward in the recipients of rejected grafts, but remained low and similar in the recipients of nonrejected allografts and those of syngeneic grafts. From days 2 to 6 the phenotype, IL-2 responsiveness, and donor-specific cytotoxic potential of the leukocytes infiltrating rejected and nonrejected allografts were comparable. On days 7 and 8, although the proportion of T cell subpopulations was identical in both combinations, activated CD4(+) graft-infiltrating cells were reduced in the nonrejected grafts. Also at this time, donor-specific cytotoxic cells were no longer detected in nonrejected grafts, whereas activity had reached a peak in the rejected grafts. These results suggest that liver grafts in both the LEW-->DA (grafts not rejected) and DA-->LEW (grafts rejected) strain combinations undergo tissue damage, but that the type of damage differs between the two combinations. Specifically, cholestasis was only observed in grafts that would subsequently be rejected. The difference in graft damage occurred at a very early time point (3 or 4 days after grafting), at which time neither the intensity nor phenotype of the graft infiltrate, its IL-2 responsiveness, or its cytotoxic potential varied between the two combinations. Thus, a lack of immune reactivity, as assessed by these parameters, does appear not to be responsible for spontaneous acceptance of liver transplants in the LEW-->DA strain combination.