Immune dysfunction in hepatitis C virus (HCV) infection
Hepatitis C virus (HCV) infection is the leading cause for chronic liver disease in the US and is associated with long-term morbidity and mortality. To develop effective therapy for this disease, it is important to understand the natural interplay between the virus and its host. In particular, it is crucial to gain insight into why the adaptive immune response cannot prevent this virus from establishing chronic infection in such a high proportion of infected individuals. The importance of antiviral CD4+ and CD8+ T cell responses in the control of viral infections is unquestioned. Chronic HCV infection is characterized by attenuated T cell responses to the virus. The enhancement of these responses appears to correlate with successful antiviral therapy. However, the mechanisms of this attenuation are poorly understood.
Recent studies show that chronic HCV-induced CD4+CD25+ regulatory T cells may play an important role in actively suppressing HCV-specific T cell responses during chronic viral infection. We hypothesize that reversal of this suppression is an important immunologic event for successful therapy, thereby allowing the upregulation and differentiation of an effective antiviral T cell responses. We further hypothesize that dysregulated antigen presentation by dendritic cells and/or B cells results in the generation of virus-specific regulatory T cells. We are attempting to dissect the immunobiology of regulatory T cells in HCV-infected individuals at different stages of disease and treatment. We want to delineate the role of APC in the generation and maintenance of these cells through the course successful versus unsuccessful therapy. Understanding such mechanisms that underlie the immune dysregulation seen in chronic HCV infection will help unveil potentially important targets for the design of rational immune-based therapy for this public health problem.
Learn More
Averill, L., Lee, W., and Karandikar, N. (2007) Differential dysfunction in dendritic cell subsets during chronic HCV infection. Clinical Immunology 123:1, 40–49.
Pillai, V., Lee, W., Theile, D., and Karandikar, N. (2007) Clinical responders to antiviral therapy of chronic HCV infection show elevated antiviral CD4+ and CD8+ T-cell responses. Journal of Viral Hepatitis, 14, 318–329.