Lymphoid dendritic cells in the liver of patients with primary biliary cirrhosis and its mouse model

Abstract An immunohistochemical survey of lymphoid dendritic cells (LDC), the most efficient antigen-presenting cells, was performed in human primary biliary cirrhosis (PBC) and in a mouse model of PBC, in order to clarify their relevance to the disease. Infiltration of interdigitating DC (IDC), a kind of LDC, into portal areas was observed throughout the progress of human PBC, but was most prominent at the beginning of the disease. The IDC expressed HLA DR and co-stimulatory molecules, B7-1 and B7-2. Likewise, N418 positive mouse LDC were found to be localized in portal areas in senescent female C57BL/6NCrj mice that spontaneously develop PBC-like liver disease. LDC were frequently observed close to the bile duct epithelia. In contrast, accumulation of LDC in portal areas was not observed in young female mice of the same strain or senescent mice of other strains which do not develop the disease. Double staining studies clarified that the LDC express MHC class II and B7-1 and B7-2, and electron microscopy studies further revealed that LDC make contact with lymphocytes. Taking these findings into account, it is conceivable that LDC infiltrate into the liver, present some unknown antigens on their surfaces, and sensitize T-cells which may eventually induce bile duct injury in PBC.