Immunohistochemical characterization of inflammatory infiltrates in primary biliary cirrhosis

— Ten liver biopsy specimens from nine patients with PBC stages II to IV were studied immunohistochemically with a broad panel of monoclonal antibodies. In areas of bile‐duct proliferation, many BA1+ B‐lymphocytes and OKT4+/Leu3a+ helper/inducer T‐cells were observed, admixed with some C 3b ‐receptor positive, mono‐and polymorphonuclear OKM1+ cells. Numerous IgM‐containing plasma cells were seen in portal tracts showing bile‐duct proliferation. In contrast, areas of piecemeal necrosis and intralobular spotty necrosis consisted mainly of OKT4+/Leu3a+ helper/inducer, and OKT8+ suppressor/cytotoxic T‐cells, admixed with some OKM1+ polymorphonuclear granulocytes. Almost no BA1+ B‐lymphocytes or Ig‐containing plasma cells were observed in areas of piecemeal necrosis and spotty necrosis. Major histocompatibility complex (MHC)‐class I antigens (i.e. HLA‐A,B,C) were demonstrated either on the liver cell membrane, or on sinusoidal lining cells. The latter also expressed MHC‐class II antigens (i.e. HLA‐DR). In two liver biopsies, an increased expression of HLA antigens was observed near areas of piecemeal and spotty necrosis. Our results indicate that several immune mechanisms each with a particular topographical distribution, are operative in PBC. Inflammatory cells, involved in humoral immunity, are present mainly in areas of bile duct proliferation. In contrast, the effector cells of antigen‐specific cellular cytotoxicity are present in areas of piecemeal necrosis and spotty necrosis. In the latter areas, a pronounced expression of MHC products representing the afferent limb of the cell‐mediated immune response, may permit an optimal T‐cell‐mediated immune effect or, eventually, result in adverse effects.