Impaired function of hepatic natural killer cells from murine chronic HBsAg carriers

Abstract

In the present study, we demonstrated hepatic NK cells in murine chronic HBsAg carriers for the first time. It was found that the number of hepatic NK cells was decreased; natural activation of hepatic NK cells was declined; and cytotoxicity of hepatic NK cells was attenuated, which might relate to the down-regulated expression of TRAIL on hepatic NK cells. Additionally, the response of hepatic NK cells to the specific stimulation of Poly (I:C) in murine chronic HBsAg carriers was changed. The increase in anti-tumor cytotoxic activity of intrahepatic activated NK cells was markedly impaired in the transgenic mice. The transgenic mice used here had high incidence of hepatocellular carcinoma, which might result from the relative weak reactivity and impaired anti-tumor activity of NK cells in the liver. Furthermore, remarkable liver injury was observed after stimulation of Poly (I:C), demonstrating the hypersensitivity to Poly (I:C) of murine chronic HBsAg carriers which might be related to the accumulated NK cells in the liver. Why the murine chronic HBsAg carriers are characterized with impaired hepatic NK cells and the implication of the impaired hepatic NK cells in pathogenesis of HBV-related diseases, such as hepatocellular carcinoma and recrudescent hepatitis, is worth of further investigating. These results of the functions of hepatic NK cells in murine chronic HBsAg carriers would contribute to interpreting the immune responses of NK cells in the liver and the immunological mechanisms of liver diseases in human chronic HBsAg carriers.