ELISPOT Analysis of Hepatitis C Virus Protein-Specific IFN-γ-Producing Peripheral Blood Lymphocytes in Infected Humans with and without Cirrhosis

An improved ability to monitor hepatitis C virus (HCV)-specific T cell immunity in infected patients may provide novel information regarding the pathogenesis and prognosis of this infection. We used an ELISPOT assay to analyze a cross-section of HCV-infected humans. HCV-infected patients without cirrhosis, those with cirrhosis, and controls with other liver diseases were tested for recall responses to HCV Core and NS3 proteins. Peripheral blood lymphocytes (PBLs) from HCV-infected patients without cirrhosis responded to NS3 and Core proteins, producing predominantly IFN-γ, with little IL-4 or IL-5. In contrast, PBLs from HCV-infected patients with cirrhosis responded to NS3, but not to the Core protein, suggesting a selectively altered immune state during cirrhosis. Our data provide support for the notion that HCV-specific IFN-γ-producing immunity is important in the pathogenesis of progressing HCV-related disease.