Lai Wai Kwan, Curbishley Stuart M, Goddard Sarah, Alabraba Edward, Shaw Jean, Youster Janine, McKeating Jane, Adams David H
Liver Research Group, Institute of Biomedical Research, The University of Birmingham Medical School, Wolfson Drive, Edgbaston, Birmingham B15 2TT, UK.
J Hepatol. 2007 Sep;47(3):338-47. doi: 10.1016/j.jhep.2007.03.024. Epub 2007 Apr 12.
BACKGROUND/AIMS: In most cases infection with hepatitis C results in chronic infection as a consequence of viral subversion and failed anti-viral immune responses. The suggestion that dendritic cells are defective in chronic HCV infection led us to investigate the phenotype and function of liver-derived myeloid (mDC) and plasmacytoid (pDC) dendritic cells in patients with chronic HCV infection.
Liver DCs were isolated without expansion in cytokines from human liver allowing us to study unmanipulated tissue-resident DCs ex vivo.
Compared with mDCs isolated from non-infected inflamed liver mDCs from HCV-infected liver (a) demonstrated higher expression of MHC class II, CD86 and CD123, (b) were more efficient stimulators of allogeneic T-cells and (c) secreted less IL-10. Reduced IL-10 secretion may be a factor in the enhanced functional properties of mDCs from HCV infected liver because antibody depletion of IL-10 enhanced the ability of mDCs from non-infected liver to stimulate T-cells. In contrast, pDCs were present at lower frequencies in HCV-infected liver and expressed higher levels of the regulatory receptor BDCA-2.
In HCV-infected liver the combination of enhanced mDC function and a reduced number of pDCs may contribute to viral persistence in the face of persistent inflammation.
背景/目的：在大多数情况下，丙型肝炎病毒感染会导致慢性感染，这是病毒颠覆和抗病毒免疫反应失败的结果。树突状细胞在慢性丙型肝炎病毒感染中存在缺陷这一观点促使我们研究慢性丙型肝炎病毒感染患者肝脏来源的髓样（mDC）和浆细胞样（pDC）树突状细胞的表型和功能。
从人肝脏中分离肝脏树突状细胞，不使用细胞因子进行扩增，这使我们能够在体外研究未受操纵的组织驻留树突状细胞。
与从未感染的炎症肝脏中分离的mDC相比，来自丙型肝炎病毒感染肝脏的mDC：（a）表现出更高的MHC II类、CD86和CD123表达；（b）是更强效的异基因T细胞刺激剂；（c）分泌的IL-10更少。IL-10分泌减少可能是丙型肝炎病毒感染肝脏中mDC功能增强的一个因素，因为用抗体去除IL-10可增强未感染肝脏中mDC刺激T细胞的能力。相比之下，pDC在丙型肝炎病毒感染肝脏中的频率较低，且表达更高水平的调节性受体BDCA-2。
在丙型肝炎病毒感染的肝脏中，mDC功能增强和pDC数量减少的组合可能在持续炎症的情况下导致病毒持续存在。
