ACUTE LIVER ALLOGRAFT-REJECTION IN THE RAT - AN ANALYSIS OF THE IMMUNE RESPONSE

Liver allografts are vigorously rejected in 9-12 days in Lewis recipie nts of fully histoincompatible DA livers. The purpose of this study wa s to examine the initial events in this cascade, specifically the role of CD4(+) T helper cells. Lewis recipients of DA or Lewis livers were killed at days 1, 2, 3, 4, and 7 days after transplant. Indicators of acute liver rejection, including a marked inflammatory infiltrate and decreased liver function, progressed in untreated recipients of allog rafts. Splenocytes taken from allogeneic recipients on days 1-4 and 7 proliferated in response to donor and third-party stimulators, whereas graft-infiltrating cells did not respond to donor and third-party ant igens until day 3 after transplant, but thereafter maintained a good r esponse. To further characterize the host T helper cell response to li ver allografts, cytokine expression was analyzed in graft tissue and i n the periphery. IL-4 mRNA was present in both syngeneic and allogenei c liver grafts, while message for IL-10 was present early in all liver grafts but persisted only in allografts. In contrast, IL-2 and IFN-ga mma transcripts were specific to rejecting allografts. Similar pattern s of cytokine expression were observed in the spleen, indicating the i mmune response to the graft involves the peripheral lymphoid organs. T hus, the cytokine profile detected during liver allograft rejection is extremely similar to that observed in other experimental models of tr ansplantation.