We have developed an in uitro system to study the interactions between biliary epithelium and lymphocytes using cultured human biliary epithelial cells. No class I1 antigens were detected by immunoperoxidase staining of the normal biliary epithelial cells, but alloactivated lymphocyte culture supernatants were able to induce class I1 expression. The activity of the supernatants was blocked with an anti-y-interferon monoclonal antibody. In addition, recombinant human y-interferon alone induced the expression of class I1 antigens and increased the intensity of class I staining of cultured biliary epithelial cells. Biliary epithelial cell-induced proliferation of alloreactive T lymphocytes demonstrated that the major histocompatibility complex molecules carry functional lymphocyteactivating determinants. The recognition of major histocompatibility complex determinants was confirmed by monoclonal antibody-blocking studies and by stimulation of an alloreactive T-cell clone. However, the biliary epithelial cells were much less potent stimulators than arterial endothelial cells tested in the same assay system. (HEPATOLOGY 1991;13:239-246.)
The biliary epithelium is a major target of lymphocytic attack in human liver allograft rejection and in many immunologically mediated liver diseases such as PBC (1,2). The immune damage in these disorders is thought to be mediated primarily by T cells. Major histocompatibility complex (MHC) antigens are likely the target of lymphocytic attack in rejection (3), and, although the target antigens in PBC have not yet been identified, the aberrant expression of class I1 antigens seen on the bile ducts in PBC livers has been hypothesized to play a role in the disease (4).
The biliary epithelium in normal livers expresses class I but not class I1 human leukocyte antigens (HLA) (5-7). However, all three class I1 subregion products, namely