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

In a model of arterialized rat liver transplantation, the biological i ndicators 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 grafti ng. 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 onwar d in the recipients of rejected grafts, but remained low and similar i n the recipients of nonrejected allografts and those of syngeneic graf ts. From days 2 to 6 the phenotype, IL-2 responsiveness, and donor-spe cific 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 nonrej ected grafts. Also at this time, donor-specific cytotoxic cells were n o 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 rejec ted) strain combinations undergo tissue damage, but that the type of d amage differs between the two combinations. Specifically, cholestasis was only observed in grafts that would subsequently be rejected. The d ifference in graft damage occurred at a very early time point (3 or 4 days after grafting), at which time neither the intensity nor phenotyp e of the graft infiltrate, its IL-2 responsiveness, or its cytotoxic p otential varied between the two combinations. Thus, a lack of immune r eactivity, as assessed by these parameters, does appear not to be resp onsible for spontaneous acceptance of liver transplants in the LEW-->D A strain combination.