My principal research activity is characterization of the cellular immune response against hepatitis C virus (HCV), specifically the role of these responses in liver injury and fibrosis. Given the lack of an animal model of liver injury due to HCV, we are utilizing different patient cohorts to…
more understand the correlation of immune responses and outcomes. We have used cohorts with rapid progression of liver disease, such as individuals co-infected with HIV and HCV, to formulate hypothesis regarding the changes in immune responses associated with liver fibrosis and then have validated these findings in other cohorts with more traditional slowly progressive disease. We are particularly interested in the interaction of this virus with the immune response in the liver, as the liver is a distinct immunologic compartment. In an order to understand why the immune response against HCV in the liver is both quantitatively and qualitatively distinct, we have used murine models to understand the interaction of hepatocytes and T cells, and have recently demonstrated that HCV accelerates apoptosis of activated T cells, which might explain the high rate of persistence. Ongoing studies are determining the mechanism of this process. We are also interested in populations of cell that are relatively enriched in the liver, including natural killer T cells, and understanding their role in viral clearance and liver fibrosis. For example, we have found that traditional phenotypic characterization of NKT substantially underestimate both the number and function of NKT cells within the liver. These studies are being expanded in the chimpanzee model of acute HCV infection in order to understand the interaction of NKT and T cells in the liver.
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