Induction of DR/IA antigens in human liver allografts. An immunocytochemical and clinicopathologic analysis of twenty failed grafts

Abstract

Twenty failed human liver allograft specimens obtained at the time of retransplantation procedures were studied using a panel of monoclonal antibodies (T11, T4, T8, NK, B1, OKM1, OKM5, Ia, DR). A clinicopathologic analysis was used to distinguish between graft failures secondary to rejection (n = 10) and those due, at least in part, to other causes (n = 10). T lymphocytes constituted the major infiltrating cellular population in the liver in rejection cases, but significant numbers of B cells and monocytes/macrophages were present also. Following transplantation, but not before, the bile duct epithelium, as well as portal and central vein and hepatic artery endothelium expressed DR/Ia antigens. These structures are preferential targets of the rejection reaction. The selective destruction of bile ducts in livers undergoing rejection was manifested in these patients by striking elevations of serum gamma glutamyl transpeptidase (GGTP) activity, a marker of biliary epithelial damage. The induced expression of DR/Ia antigens on structures targeted for immune destruction may be an important event in the pathogenesis of liver allograft rejection.

Figure 1

(a) T lymphocytes (T11⁺) in the portal tract from case 1. Note the cells beneath the portal vein (PV) endothelium (large arrowhead), surrounding bile ductules (arrow), and relative restriction of T11⁺ cells to the portal tracts (T11 IPEX, hematoxylin; ×125). (b) Higher power (500×) of the above specimen showing T cells adjacent to and infiltrating a small bile ductule sectioned longitudinally (out-lined by arrows). (c) T cell lymphocytes (T11⁺) in liver tissue from case 4 showing tight clustering of inflammatory cells surrounding a small bile ductule (arrow, 250×). (d) Liver tissue from case 2 stained for Ia antigen, showing positivity in larger septa1 bile duct (BD), endothelium of hepatic artery (HA, arrowhead) and small bile ductuler, (arrows), which are surrounded by inflammatory cells (125×). (e) B lymphocyte (B1⁺) in a portal tract from case 7 showing a nodule of B cells. Bile ductules could not be seen in this portal tract (315×). (f) OKMl⁺ cells in tissue from case 13 showing numerous positive cells in the portal tracts. This case was complicated by sepsis and bacterial cholangitis (125×).