期刊
JOURNAL OF HEPATOLOGY
卷 48, 期 1, 页码 51-60出版社
ELSEVIER
DOI: 10.1016/j.jhep.2007.08.008
关键词
hepatitis C virus; core protein; hepatocytes; myeloid dendritic cells; T cell priming; MHC class I molecules; costimulatory molecules; regulatory T cells
Background/Aims: Hepatitis C virus leads to chronic hepatitis in the majority of infected individuals. The mechanism of viral persistence is not completely understood. Hepatitis C virus core protein is produced within hepatocytes and is secreted during HCV infection. Our study characterizes the effects of core protein on T cell priming in mice. Methods: We used a system of antigen-specific in vitro priming of CD4(+) and CD8(+) T cells by myeloid dendritic cells, hepatoma cells or primary hepatocytes. Core protein was either added to the cultures or expressed by antigen-presenting cells. Results: Antigen-presenting cells treated with core protein showed reduced surface expression of major histocompatibility molecules. Myeloid dendritic cells showed also reduced expression of costimulatory molecules. CD4(+) and CD8(+) T cells primed by these cells showed defects in activation, proliferation, and cytokine production. Importantly, CD4(+) and also CD8(+) T cells primed in the presence of core protein showed an increase in interleukin-10 production resembling the phenotype of regulatory T cells. Conclusions: Hepatitis C virus core protein inhibits priming of antigen-specific CD4(+) and CD8(+) T cell responses by downregulation of major histocompatibility molecules and costimulatory molecules on antigen-presenting cells and induces development of IL-10-producing T cells. (c) 2007 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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