Impaired function of dendritic cells circulating in patients infected with hepatitis C virus who have persistently normal alanine aminotransferase levels.
Hepatitis C virus (HCV) induces chronic liver disease in hosts which can eventually progresses to liver cirrhosis and hepatocellular carcinoma. However, progression of liver disease is slower in patients with persistently normal levels of alanine aminotransferase (ALT) than in those with active hepatitis. Although distinct immune responses against HCV have been proposed in asymptomatic infection, the role of circulating dendritic cells (DC) in the pathogenesis of these patients remains obscure. To address this issue, we compared the number and function of myeloid DC (MDC) and plasmacytoid DC (PDC) between uninfected individuals and HCV-infected patients with or without elevated ALT levels. Numbers of DC and DC progenitors were significantly lower in patients with chronic active hepatitis than in control subjects. However, no differences were found in the number of DC between normal controls and HCV-infected patients with persistently normal ALT levels. MDC from patients with active hepatitis were less able to polarize naive CD4 T cells into the Th1 phenotype, while their MDC and PDC primed more CD4 T cells producing IL-10 than those from normal controls. Such dysfunction of DC was also observed in patients with persistently normal ALT levels. In conclusion, circulating DC decrease in number predominantly in HCV-infected patients with active hepatitis, and the function of DC is impaired even in those with normal ALT levels.
Kanto
Tatsuya
T
Department of Molecular Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Inoue
Michiyo
M
Miyazaki
Masanori
M
Itose
Ichiyo
I
Miyatake
Hideki
H
Sakakibara
Mitsuru
M
Yakushijin
Takayuki
T
Kaimori
Aki
A
Oki
Chika
C
Hiramatsu
Naoki
N
Kasahara
Akinori
A
Hayashi
Norio
N
D000410:Alanine Transaminase / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002452:Cell Count; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D005260:Female; D006526:Hepatitis C / Q000097:blood / Q000276:immunology / Q000503:physiopathology*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D022423:Myeloid Cells / Q000166:cytology; D010950:Plasma Cells / Q000166:cytology; D013234:Stem Cells / Q000166:cytology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000410:Alanine Transaminase