Differential Dysfunction of Dendritic Cells and B-cells During Chronic HCV Infection (46.11)

Abstract

Abstract Chronic hepatitis C virus (HCV) infection is characterized by attenuated antiviral T cell responses. We hypothesized that HCV-associated dysfunction of antigen presenting cells (APC) may be responsible, in part, for such attenuation. We evaluated the function and phenotype of dendritic cells (myeloid vs. plasmacytoid), B cells, and monocytes, finding distinct functional differences among the APC subsets. Myeloid DC (MDC) from chronic HCV patients showed slightly lower APC capacity with lower HLA-DR and CD86 expression. HCV-MDC also had a tendency to secrete more IL-10, when compared to healthy MDC. On the other hand, HCV-plasmacytoid DC (PDC) showed a significantly reduced ability to make IFN-α. B cells from HCV patients had a hyperactivated phenotype and a marked enhanced APC capacity. Interestingly, the enhanced B cell APC function correlated with detection of virus in these cells. Finally, increased APC functionality was paradoxically associated with the generation of a higher proportion of induced regulatory T-cells, providing a plausible explanation for T-cell attenuation. In conclusion, our studies underscore the necessity to dissect APC subsets for functional perturbations and provide evidence for their role in the immune attenuation accompanying chronic HCV infection.