Acute Hepatitis C Virus [HCV] infection commonly results in chronic persistence (50-90%), making HCV the most common cause of chronic viral hepatitis. There are nearly 4 million Americans chronically infected with HCV (roughly four times the number of HIV infected individuals).
The long-term risk of cirrhosis with chronic HCV infection is estimated at 20%, with subsequent increases in the risk for liver failure and hepatocellular carcinoma. Evidence suggests that HCV-specific T cell immunity contributes to the pathogenesis of HCV mediated disease, participating in favorable clinical outcome as well as in organ damage.
Our researchers at the CWRUmedicine Division of Rheumatic Diseases have observed a relative paucity of HCV specific effector T cells in freshly prepared PBMC from subjects with chronic HCV infection, contrasting with normal frequencies of effector T cells specific for other antigens in the same subjects. These data are consistent with the notion that circulating HCV specific T cells are deficient in effector function, number, or both, while HCV infection does not result in generalized dysfunction of T cells with other specificities. Though the mechanism for the antigen specific dysfunction in HCV infection is unclear, one possible mechanism is abnormal priming and stimulation of HCV specific T cell populations by dysfunctional HCV containing antigen presenting cell (APC) populations. We hypothesize that one consequence of HCV infection is altered DC function. In addition HCV infection may affect T-cell responsiveness to normal functioning DC. To address this hypothesis we will A)Determine the impact of HCV infection on DC phenotype and function; B) Determine the impact of HCV on T cells by characterizing T cell responsiveness in HCV infected and healthy control subjects; and C. Determine the effects of HCV proteins and virus as a direct inhibitor DC function.
Learn more about our researchers and the role of immature dendritic cells in host defense against HCV [Hepatitis C Virus] infection at CWRUmedicine.org