These immune evasion strategies include: disease mutation, main 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]

These immune evasion strategies include: disease mutation, main 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]. from immunized mice. On the other hand, the percentages of CD4+and CD8+T cells in the non-transgenic recipient mouse lymph nodes were significantly higher than the transgenic mice when they received the adoptive transfer from immunized donors. Interestingly, livers of transgenic mice that received transfers from immunized mice experienced a significantly higher percentage of CFSE labeled T cells than livers of non-transgenic mice receiving non-immunized transfers. == Conclusions == These results suggest that the T cells from HCV immunized mice identify the HCV proteins in the liver of the transgenic mouse model and homed to the HCV antigen manifestation sites. We propose by using this model system to study active T cell responses in HCV illness. == Intro == Hepatitis C disease (HCV) is a major cause of chronic liver disease worldwide. The disease causes chronic illness in 80% of acutely HCV-infected individuals; a subset of these individuals develop progressive liver injury leading to liver cirrhosis and/or hepatocellular carcinoma [1,2]. Immune responses to HCV perform important functions at various phases of the illness. There is growing evidence that the ability of acutely HCV-infected individuals to control the primary HCV illness depends on the vigorous cellular immune reaction to the disease [3]. In the chronic phase of illness, immune responses determine the pace of progression of disease, both by limiting viral replication and by contributing to immunopathology. Livers from chronically HCV-infected individuals show T cell infiltration; however, these cells are not HCV specific and Rabbit Polyclonal to FZD4 are unable to eradicate the disease [4]. These liver-infiltrating lymphocytes are associated with liver damage in chronic HCV illness via mechanisms that are not well recognized [5]. There are several immune evasion mechanisms, which might clarify the ability of the disease to escape the immune responses and establish a prolonged illness. These immune Atractylenolide III evasion strategies include: disease mutation, main T cell response failure, impairment of antigen demonstration, suppression of T cell function by HCV proteins, impairment Atractylenolide III of T cell maturation and a tolerogenic environment in the liver [6]. However, the immunological basis for the inefficiency of the cellular defense response in chronically infected persons is not well recognized. Cellular immune responses play a critical role in liver damage during the clinical course of hepatitis C illness. HCV-specific CD4+T cells are involved in eradication of the disease in acute illness but their responses are fragile and insufficient in chronic hepatitis [7]. However, there is no very clear evidence that CD4+T cells play a direct role in the liver injury observed during chronic HCV illness. CD4+T cells activate the CD8+cytotoxic T lymphocyte (CTL) response, which eradicates the virus-infected cells either by inducing apoptosis (cytolytic mechanism) or by generating interferon-gamma (IFN-), which suppresses the viral replication (non-cytolytic mechanism) [8]. Atractylenolide III Enhanced hepatocyte apoptosis leads to liver damage in chronic HCV infections [9]. HCV-specific CD8+CTL responses are Atractylenolide III compromised in most individuals who fail to very clear the infection. In addition, those cells have a diminished capacity to proliferate and create less IFN- in response to HCV antigens [10]. Those inefficient CD8+T cell responses mediate HCV-related liver damage and are inadequate at clearing the chronic illness. The mechanisms responsible for immune-mediated liver damage associated with HCV are poorly understood. One of the mechanisms for liver damage is that the Atractylenolide III HCV-activated T cells communicate the Fas ligand in the cell surface, that may bind with the Fas receptor on hepatocytes, initiatiating Fas-mediated signaling, which may then lead to cell death [11]. HCV core protein increases the manifestation of Fas ligand on the surface of liver-infiltrating T cells leading to the induction of hepatic swelling and liver damage [12,13]. Another important mechanism of immune-mediated liver damage is definitely through CD8+T cell-mediated cytolysis. Earlier studies on concanavalin-A-induced hepatitis have demonstrated that CD8+T cells can kill the prospective cellsin vivoby cytolytic mechanisms mediated by perforin [14] or requiring IFN- [15]. This may.