TY - JOUR
T1 - Hepatitis C virus core protein impairs in vitro priming of specific T cell responses by dendritic cells and hepatocytes
AU - Zimmermann, Mona
AU - Flechsig, Christin
AU - Monica, Nicola La
AU - Tripodi, Marco
AU - Adler, Guido
AU - Dikopoulos, Nektarios
PY - 2008/1
Y1 - 2008/1
N2 - 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.
AB - 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.
KW - Core protein
KW - Costimulatory molecules
KW - Hepatitis C virus
KW - Hepatocytes
KW - MHC class I molecules
KW - Myeloid dendritic cells
KW - Regulatory T cells
KW - T cell priming
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U2 - 10.1016/j.jhep.2007.08.008
DO - 10.1016/j.jhep.2007.08.008
M3 - Article
C2 - 17998148
AN - SCOPUS:36549060584
VL - 48
SP - 51
EP - 60
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 1
ER -