Ultrastructural immunocytochemical analysis of lymphocytes infiltrating bile duct epithelia in primary biliary cirrhosis.

Subpopulations of lymphocytes in portal areas, especially infiltrating bile duct epithelia were analyzed by light and electron microscopy using indirect peroxidase-labeled antibody method and monoclonal antibodies against pan-T (Leu 1), cytotoxic/suppressor T (Leu 2a), helper/inducer T (Leu 3a) and natural killer/K (Leu 7) and suppressor T (Leu 15) cells in liver biopsy specimens from four patients with primary biliary cirrhosis. Bile ducts with chronic nonsuppurative destructive cholangitis were observed in two patients. Leu 1+ and Leu 2+ cells were frequently seen in intimate contact with epithelial ductal cells. The majority of intraepithelial cells possessing Leu 2a antigen did not react with anti-Leu 15 antibody. Leu 3a+ or Leu 7+ cells seldom infiltrated ductal epithelia. These findings indicate that the majority of intraepithelial lymphocytes in bile ducts most likely represent Leu 2a+15- cytotoxic T cells. By immunoelectron microscopy, Leu 1+ or Leu 2a+ lymphocytes often breached the basement membrane of bile ducts and were present within dilated intercellular spaces between biliary epithelial cells. Furthermore, they often formed sharp or broad contacts with the epithelial cells, and occasionally pseudopods projecting from the surfaces of Leu 2a+ cells extended into the epithelial cells. Most of Leu 2a+ lymphocytes contained little cytoplasm with few granules and a small Golgi apparatus. Such findings suggest that cytotoxic T cells may contribute to the pathogenesis of chronic nonsuppurative destructive cholangitis in primary biliary cirrhosis.