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Published on: February 19, 2019
Circulating Valpha24+Vbeta11+ NKT cell numbers and dendritic cell CD1d expression in hepatitis C virus infected
Hans J J van der Vliet1, Johan W Molling, B Mary E von Blomberg
1Department of Internal Medicine, Vrije Universiteit Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. jj.vandervliet@vumc.nl
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 alpha-galactosylceramide (alpha-GalCer, KRN7000). Previous studies have indicated that alpha-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 Valpha24+Vbeta11+ 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 Valpha24+Vbeta11+ 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 Valpha24+Vbeta11+ NKT cell ligand alpha-GalCer in HCV-infected patients are present.
Insights
Circulating natural killer T (NKT) cell numbers are not reduced in hepatitis C virus (HCV) infection. CD1d expression remains comparable, suggesting NKT cell therapy potential for HCV patients.
Area of Science:
- Immunology
- Virology
- Hepatology
Background:
- Natural killer T (NKT) cells regulate immune responses and can inhibit viral replication.
- Activation of NKT cells by alpha-galactosylceramide (alpha-GalCer) requires CD1d expression and sufficient NKT cell numbers.
- Previous research shows conflicting data on invariant Valpha24+Vbeta11+ NKT cell counts in hepatitis C virus (HCV) infection.
Purpose of the Study:
- To investigate the circulating numbers of invariant Valpha24+Vbeta11+ NKT cells in patients with active HCV infection.
- To assess the expression levels of CD1d on antigen-presenting cells in HCV-infected individuals.
- To determine the feasibility of evaluating alpha-GalCer's antiviral effects in HCV.
Main Methods:
- Cross-sectional and longitudinal analysis of patients with HCV undergoing antiviral therapy.
- Quantification of circulating Valpha24+Vbeta11+ NKT cells.
- Assessment of CD1d expression on peripheral blood monocytes and CD1c+ myeloid dendritic cells (DCs) in healthy and HCV-infected individuals.
Main Results:
- Circulating Valpha24+Vbeta11+ NKT cell numbers were not decreased in active HCV infection.
- CD1d expression levels were comparable between healthy individuals and HCV-infected patients on monocytes and myeloid DCs.
- The necessary components for NKT cell-based therapy evaluation are present in HCV patients.
Conclusions:
- Active HCV infection does not lead to a reduction in circulating invariant Valpha24+Vbeta11+ NKT cells.
- Sufficient CD1d expression on antigen-presenting cells in HCV patients supports potential therapeutic strategies.
- These findings pave the way for exploring alpha-GalCer's efficacy against HCV.

