Hepatitis C virus core protein impairs in vitro priming of specific T cell responses by dendritic cells and hepatocytes.
OBJECTIVE
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.
Zimmermann
Mona
M
Department of Internal Medicine I, University of Ulm, Germany.
Flechsig
Christin
C
La Monica
Nicola
N
Tripodi
Marco
M
Adler
Guido
G
Dikopoulos
Nektarios
N
D000818:Animals; D039521:CD11c Antigen / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005805:Genes, MHC Class I / Q000235:genetics / Q000276:immunology; D005802:Genes, MHC Class II / Q000235:genetics / Q000276:immunology; D022781:Hepatocytes / Q000276:immunology*; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010641:Phenotype; D010957:Plasmids / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D014162:Transfection; D014758:Viral Core Proteins / Q000235:genetics* / Q000276:immunology*
D039521:CD11c Antigen; D016207:Cytokines; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D010047:Ovalbumin