Circulating Vα24+Vβ11+ NKT cell numbers and dendritic cell CD1d expression in hepatitis C virus infected patients

Abstract: CD1d-restricted natural killer T (NKT) cells are involved in the regulation of various immune responses, and have been shown to inhibit viral replication in animal hepatitis models when activated by the glycolipid α-galactosylceramide (α-GalCer, KRN7000). Previous studies have indicated that α-GalCer-induced activation of the immune system requires both CD1d expression by antigen-presenting cells as well as (normal) numbers of NKT cells. Discrepancies exist over circulating numbers of human invariant Vα24+Vβ11+ NKT cells during hepatitis C virus (HCV) infection. Here, by cross-sectional analysis and longitudinal analysis of patients undergoing effective combination antiviral therapy, we demonstrate that circulating Vα24+Vβ11+ NKT cell numbers are not decreased during active HCV infection. Importantly, as we also show that CD1d is expressed at comparable levels by peripheral blood monocytes and CD1c+ myeloid dendritic cells (DC) of healthy individuals and HCV-infected patients, these data indicate that all ingredients for evaluating the antiviral effects of the Vα24+Vβ11+ NKT cell ligand α-GalCer in HCV-infected patients are present. [Copyright &y& Elsevier]