Investigation of the CD4+ T lymphocyte responses to Hepatitis C virus infection : cytokine production and its relationship to fibrosis and inflammation

This study investigated the phenotype and magnitude of the CD4+ T lymphocyte response to HCV to see if there was any correlation with the severity of the resultant liver disease. In addition, genetic markers which could influence the CD4+ T lymphocyte response were examined for correlation with severity of liver disease. Finally, the effect of the HCV specific CD4+ T lymphocyte response on the effector cells of hepatic fibrosis, hepatic stellate cells, was investigated. Genomic DNA from CHC patients was tested for the presence of the allele HLA DQB1*0301, a Major Histocompatibility Complex class II molecule which has been shown to be over-represented in individuals with evidence of spontaneous resolution of acute infection. There was no correlation between frequency of this allele in our population and severity of CHC related liver disease. However, analysis of clinical information gathered from these patients confirmed that age, duration of infection and excess alcohol intake were all risk factors for more severe liver disease. In addition, severity of fibrosis correlated positively with severity of inflammation; supporting the hypothesis that fibrosis is the result of chronic inflammation of CHC. Functional studies of the CD4+ T lymphocyte response in HCV infection confirmed that HCV lymphocyte proliferative responses are different between CHC patients and those with evidence of spontaneous resolution of HCV infection. There were no differences in the HCV specific proliferative responses between groups of CHC patients discordant for severity of liver disease. However, HCV specific Interferon-γ secretion was more commonly seen in patients with severe liver disease. CD4+ T lymphocyte responses to non-HCV recall antigens were identical between all groups.