1,720,976 research outputs found
Proteasomal antigen-processing is regulated by cytokines of the innate immune response in acute HCV infection
No full textDelayed induction not impaired recruitment of HCV-specific CD8 T cells is resonsible for the late onset of acute hepatitis
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Trafficking of HCV-specific CD8 T cells to the liver in the early phase of acute hepatitis C
No full textLiver-directed gamma interferon gene delivery in chronic hepatitis C
No full textGamma interferon (IFN-gamma) has been shown to inhibit replication of subgenomic and genomic hepatitis C virus (HCV) RNAs in vitro and to noncytolytically suppress hepatitis B virus (HBV) replication in vivo. IFN-gamma is also known for its immunomodulatory effects and as a marker of a successful cellular immune response to HCV. Therapeutic expression of IFN-gamma in the liver may therefore facilitate resolution of chronic hepatitis C, an infection that is rarely resolved spontaneously. To analyze immunomodullatory and antiviral effects of liver-specific IFN-gamma expression in vivo, we intravenously injected two persistently HCV-infected chimpanzees twice with a recombinant, replication-deficient HBV vector and subsequently with a recombinant adenoviral vector. These vectors expressed human IFN-gamma under control of HBV- and liver-specific promoters, respectively. Gene transfer resulted in a transient increase of intrahepatic IFN-gamma mRNA, without increase in serum alanine aminotransferase levels. Ex vivo analysis of peripheral blood lymphocytes demonstrated enhanced CD16 expression on T cells and upregulation of the liver-homing marker CXCR3. Moreover, an increased frequency of HCV-specific T cells was detected ex vivo in the peripheral blood and in vitro in liver biopsy-derived, antigen-nonspecifically expanded T-cell lines. None of these immunologic effects were observed in the third chimpanzee injected with an HBV control vector. Despite these immunologic effects of the experimental vector, however, IFN-gamma gene transfer did not result in a significant and long-lasting decrease of HCV titers. In conclusion, liver-directed IFN-gamma gene delivery resulted in HCV-specific and nonspecific activation of cellular immune responses but did not result in effective control of HCV replication
CD8 T cells are recruited to the liver in acute hepatitis C by HCV RNA-induced CXCR3- and CCR5-ligands
No full textDelayed induction not impaired recruitment of HCV-specific CD8 T cells is resonsible for the late onset of acute hepatitis
No full textCD8 T cells are recruited to the acutely HCV-infected liver by HCV RNA-induced CXCR3- and CCR5-ligands
No full textCytoplasmic tubular structures in liver of HBsAg carrier chimpanzees infected with delta agent and comparison with cytoplasmic structures in non-A, non-B hepatitis
No full textHepatitis C virus (HCV) RNA-induced chemokine expression and their roles in acute HCV infection
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