Hepatitis C virus core protein impairs in vitro priming of specific T cell responses by dendritic cells and hepatocytes☆

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.

Keywords: Hepatitis C virus, Core protein, Hepatocytes, Myeloid dendritic cells, T cell priming, MHC class I molecules, Costimulatory molecules, Regulatory T cells