Reduced numbers and impaired ability of myeloid and plasmacytoid dendritic cells to polarize T helper cells in chronic hepatitis C virus infection.
Hepatitis C virus (HCV) infection induces a wide range of chronic liver injuries. The mechanism by which HCV evades the immune surveillance system remains obscure. Blood dendritic cells (DCs) consist of myeloid and plasmacytoid subsets that play distinct roles in the regulation of antivirus immune responses; however, their roles in the pathogenesis of HCV infection are yet to be determined. We compared the numbers and functions of myeloid and plasmacytoid DCs between 43 patients with chronic hepatitis and 26 age-matched healthy volunteers. Absolute numbers of myeloid DCs, plasmacytoid DCs, and DC progenitors in the periphery were significantly lower in patients with chronic hepatitis than in healthy volunteers. Myeloid and plasmacytoid DCs from the patients had impaired abilities to stimulate allogeneic CD4 T cells and to produce interleukin (IL)-12 p70 and interferon- alpha , compared with those from healthy volunteers. After exposure to naive CD4 T cells, myeloid DCs from the patients were less able to drive the T helper type 1 response, whereas myeloid and plasmacytoid DCs from the patients primed more IL-10-producing cells than did those from healthy volunteers. In conclusion, in chronic HCV infection, both types of blood DCs are reduced and have an impaired ability to polarize T helper cells.
Kanto
Tatsuya
T
Department of Molecular Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. kantot@moltx.med.osaka-u.ac.jp
Inoue
Michiyo
M
Miyatake
Hideki
H
Sato
Aki
A
Sakakibara
Mitsuru
M
Yakushijin
Takayuki
T
Oki
Chika
C
Itose
Ichiyo
I
Hiramatsu
Naoki
N
Takehara
Tetsuo
T
Kasahara
Akinori
A
Hayashi
Norio
N
D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D018664:Interleukin-12 / Q000032:analysis; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
D016898:Interferon-alpha; D016753:Interleukin-10; D018664:Interleukin-12