Analysis of cellular immune responses in perihperal blood and liver tissues in HCV infection

点击翻译按钮获取中文摘要

Hepatitis C virus (HCV) infection frequently persists, progresses to chronic hepatitis and cirrhosis, and finally develops hepatocellular carcinoma. Although viruses in the infected cells are eliminated by virus-specific cytotoxic T lymphocytes (CTLs) that recognize endogenously synthesized, processed viral proteins presented by HLA and lyse the cells, the CTL responses are regulated by helper T cells and immunomodulatory cytokines. In the present study, we investigated mainly the helper T cell and immunomodulatory cytokine responses in peripheral blood ant liver tissues of patients with chronic HCV infection. In chronic HCV infection, type 1 helper T cell responses that produced interferon-γin response to HCV proteins dominated type 2 helper T cell responses that produced interleukin-4. However, HCV proteins stimulated the production of immunosuppressive interleukin-10. In the peripheral blood of patients with chronic hepatitis C, the number of HCV-stimulated interleukin-10-producing cells was larger than that of HCV-stimulated interferon-γ-producing cells. Thus, the anti-HCV responses seemed to be suppressed in the peripheral blood. HCV-specific helper T cells were concentrated in the liver tissues. The number of HCV-stimulated interferon-γ-producing cells in the peripheral blood was inversely correlated with serum HCV RNA levels. Interferon treatment decreased the number of peripheral blood HCV-stimulated interferon-γ-producing cells at 3 month, but the number returned to the pretreatment level later. There were regions in HCV proteins that stimulated of production of interferon-γ and interleukin-10 by peripheral blood mononuclear cells of patients with chronic HCV infection in common. Finally we identified an epitope in HCV recognized by CTLs in association with HLA-A^*0206.