Decreased interferon-alpha production and impaired T helper 1 polarization by dendritic cells from patients with chronic hepatitis C.
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)-alpha 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-alpha. The capacity of DCs to induce polarization of autologous naive CD4(+) T lymphocytes to IFN-gamma-producing effector T lymphocytes was also assessed. The frequencies of PDCs producing intracellular IFN-alpha (P < 0.01) and the levels of IFN-alpha 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)/ micro l, median (interquartile range), n = 63) compared to normal control (11.7 (7.8)/ micro l, n = 34) (P < 0.01). Moreover, DCs from patients with CHC induced significantly lower numbers of IFN-gamma-producing effector T lymphocytes compared to that of controls (P < 0.01). This study indicates that the low IFN-alpha-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.
Third Department of Internal Medicine, Ehime University School of Medicine, Japan.
H
H
Murakami
S M F
SM
Akbar
H
H
Matsui
N
N
Horiike
M
M
Onji
D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D018417:Th1 Cells / Q000276:immunology*
D007371:Interferon-gamma