hcv+ hepatocytes induce human regulatory cd4+ t cells through the production of tgf-β丙肝病毒+肝细胞诱导人类管理通过生产tgf-βcd4 + t细胞.pdfVIP

HCV+ Hepatocytes Induce Human Regulatory CD4+ T Cells through the Production of TGF-b 1 1 1 1,2 Caroline H. T. Hall , Rachel Kassel , Robert S. Tacke , Young S. Hahn * 1 Department of Microbiology, Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia, United States of America, 2 Department of Pathology, University of Virginia, Charlottesville, Virginia, United States of America Abstract Background: Hepatitis C Virus (HCV) is remarkably efficient at establishing persistent infection and is associated with the development of chronic liver disease. Impaired T cell responses facilitate and maintain persistent HCV infection. Importantly, CD4+ regulatory T cells (Tregs) act by dampening antiviral T cell responses in HCV infection. The mechanism for induction and/or expansion of Tregs in HCV is unknown. Methodology/Principal Findings: HCV-expressing hepatocytes were used to determine if hepatocytes are able to induce Tregs. The infected liver environment was modeled by establishing the co-culture of the human hepatoma cell line, Huh7.5, containing the full-length genome of HCV genotype 1a (Huh7.5-FL) with activated CD4+ T cells. The production of IFN-c was diminished following co-culture with Huh7.5-FL as compared to controls. Notably, CD4+ T cells in contact with Huh7.5-FL expressed an increased level of + the Treg markers, CD25, Foxp3, CTLA-4 and LAP, and were able to suppress the proliferation of effector T cells. Importantly, HCV hepatocytes upregulated the production of TGF-b and blockade of TGF-b abrogated Treg phenotype and function.