Kanto Tatsuya, Inoue Michiyo, Miyatake Hideki, Sato Aki, Sakakibara Mitsuru, Yakushijin Takayuki, Oki Chika, Itose Ichiyo, Hiramatsu Naoki, Takehara Tetsuo, Kasahara Akinori, Hayashi Norio
Department of Molecular Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
J Infect Dis. 2004 Dec 1;190(11):1919-26. doi: 10.1086/425425. Epub 2004 Oct 27.
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.
丙型肝炎病毒（HCV）感染可引发多种慢性肝损伤。HCV逃避免疫监视系统的机制仍不清楚。血液中的树突状细胞（DCs）由髓样和浆细胞样亚群组成，它们在抗病毒免疫反应的调节中发挥着不同的作用；然而，它们在HCV感染发病机制中的作用尚待确定。我们比较了43例慢性肝炎患者和26名年龄匹配的健康志愿者之间髓样和浆细胞样DCs的数量和功能。慢性肝炎患者外周血中髓样DCs、浆细胞样DCs和DC祖细胞的绝对数量显著低于健康志愿者。与健康志愿者相比，慢性肝炎患者的髓样和浆细胞样DCs刺激同种异体CD4 T细胞以及产生白细胞介素（IL）-12 p70和α干扰素的能力受损。在接触初始CD4 T细胞后，慢性肝炎患者的髓样DCs驱动1型辅助性T细胞反应的能力较弱，而慢性肝炎患者的髓样和浆细胞样DCs诱导产生IL-10的细胞比健康志愿者更多。总之，在慢性HCV感染中，两种类型的血液DCs数量均减少，且极化辅助性T细胞能力受损。
