Decreased interferon-α production and impaired T helper 1 polarization by dendritic cells from patients with chronic hepatitis C

Abstract

SUMMARY Patients with chronic hepatitis C (CHC) are unable to prime and maintain vigorous T cell responses that are initiated during the acute phase of hepatitis C virus (HCV) infection. As dendritic cells (DCs) induce and regulate both innate and adaptive immune responses, the aim of this study was to analyse two critical functions of DCs: firstly, production of interferon (IFN)-α and, secondly, polarization of T helper 1 lymphocytes. The frequencies of plasmacytoid DC (PDC) and myeloid DC (MDC) were estimated in 63 patients with CHC and 34 normal controls using four-colour flow cytometry. Circulating DCs were isolated from peripheral blood of CHC patients (n = 10) and normal controls (n = 10). These DCs were cultured with herpes simplex virus-1 to evaluate their capacity to produce IFN-α. The capacity of DCs to induce polarization of autologous naive CD4+ T lymphocytes to IFN-γ-producing effector T lymphocytes was also assessed. The frequencies of PDCs producing intracellular IFN-α (P < 0·01) and the levels of IFN-α in culture supernatant of PDCs (P < 0·01) were significantly lower in patients with CHC compared to those of normal controls. The numbers of MDC were significantly lower in patients with CHC (8·2 (6·0)/µl, median (interquartile range), n = 63) compared to normal control (11·7 (7·8)/µl, n = 34) (P < 0·01). Moreover, DCs from patients with CHC induced significantly lower numbers of IFN-γ-producing effector T lymphocytes compared to that of controls (P < 0·01). This study indicates that the low IFN-α-producing capacity and impaired T helper 1 polarization ability of DCs from patients with CHC might be responsible for the typical low anti-HCV immune responses in these patients.