There are several immune evasion mechanisms,

which might explain the ability of the virus to escape the immune responses and establish a persistent infection. These immune evasion strategies include: virus mutation, primary T cell response failure, impairment of antigen presentation, suppression of T cell function by HCV proteins, impairment of T cell maturation and a tolerogenic environment in the liver [6]. Nevertheless, the immunological basis for the inefficiency of the cellular immune response in chronically infected persons is not well understood. Cellular immune responses play a critical role in liver damage during the clinical course of hepatitis C infection. HCV-specific CD4+ T cells are involved in eradication of the virus in acute infection but their responses are weak and insufficient in chronic hepatitis Blasticidin S order [7]. However, there is no clear evidence that CD4+ T cells play a direct role in the liver injury observed during chronic HCV infection. CD4+ T cells activate

the CD8+ cytotoxic T lymphocyte (CTL) response, which eradicates the virus-infected cells either by inducing Proteases inhibitor apoptosis (cytolytic mechanism) or by producing interferon-gamma (IFN-γ), which suppresses the viral replication (non-cytolytic mechanism) [8]. Enhanced hepatocyte apoptosis leads to liver damage in chronic HCV infections [9]. HCV-specific CD8+ CTL responses are compromised in most patients who fail to clear the infection. In addition, selleck kinase inhibitor those cells have a diminished capacity to proliferate and produce less IFN-γ in response to HCV antigens [10]. Those inefficient Carnitine dehydrogenase CD8+ T cell responses mediate HCV-related liver damage and are inadequate at clearing the chronic infection. The mechanisms responsible for immune-mediated liver damage associated with HCV are poorly understood. One of the mechanisms for liver damage is that the HCV-activated T cells express the Fas ligand at the cell surface, which will bind with the Fas receptor on hepatocytes, initiatiating Fas-mediated signaling, which may then lead to cell death [11]. HCV core protein increases the

expression of Fas ligand on the surface of liver-infiltrating T cells leading to the induction of hepatic inflammation and liver damage [12, 13]. Another important mechanism of immune-mediated liver damage is through CD8+ T cell-mediated cytolysis. Previous studies on concanavalin-A-induced hepatitis have demonstrated that CD8+ T cells can kill the target cells in vivo by cytolytic mechanisms mediated by perforin [14] or requiring IFN-γ [15]. This may also involve additional molecules such as TNF-α [16]; therefore, the level of cytolytic activity or expression of cytolysis mediators from the infiltrating lymphocytes could be a determinant for induction of immune-mediated liver damage. It is still controversial whether the liver damage associated with hepatitis C infection is due to the viral cytopathic effects or due to the immune response mediated damage.