Increased activated natural killer T cells in the liver of patients with advancedstage primary biliary cirrhosis

Abstract

Although growing evidence suggests a major role for T cells in the pathogenesis of primary biliarycirrhosis (PBC), the roles of natural killer (NK) and natural killer T (NKT) cells, which predominatein the liver, in the pathogenesis of PBC remain unclear. We investigated the status ofNK and NKT cells in the liver and peripheral blood samples obtained from 11 patients with asymptomaticPBC diagnosed as stage I or II (early PBC) and 7 patients with symptomatic PBCwho underwent liver transplantation (advanced PBC) using flow cytometry and immunohistochemicalstaining. The proportions of NK and NKT cells were significantly decreased in the liver ofpatients with early PBC compared with normal donors. However, the proportion of CD56+ NKTcells was increased in the liver of patients with advanced PBC. Moreover, the proportion of activatedFas ligand (FasL)-positive NKT cells was significantly increased in the liver of patients withadvanced PBC compared with early PBC (P = 0.013). We also found increased expression of FasLon lymphocytes infiltrating around the injured bile duct in advanced PBC using immunohistochemicalstaining. Our results suggest that activated NKT cells may contribute to the biliary epithelialcell death resulting in the progression of PBC.