Pachiadakis Ioannis, Chokshi Shilpa, Cooksley Helen, Farmakiotis Dimitrios, Sarrazin Christoph, Zeuzem Stefan, Michalak Tomasz I, Naoumov Nikolai V
Institute of Hepatology, University College London, London, UK.
Clin Immunol. 2009 Jun;131(3):415-25. doi: 10.1016/j.clim.2009.02.001. Epub 2009 Mar 20.
Plasma and cellular HCV RNA and core antigen were tested in monocyte-derived DC (MDDC) from chronic hepatitis C patients undergoing treatment with peg-interferon alpha2b/ribavirin. DC allostimulatory capacity, HCV-specific T-cell reactivity and IL-12 production were measured at baseline and treatment week (TW)12. Using DC and autologous CD4(+)T-cells, obtained at baseline and TW12, we performed cross-over experiments to determine the relative role of DC and/or T-cells for impaired immune reactivity to HCV. HCV RNA and HCV core plasma levels had an impact on DC phenotype and allostimulatory capacity. In contrast, HCV genome/core protein, although detectable in DC from some patients had no effect on DC function. Antiviral immunity at TW12 was not improved in patients who remained HCV RNA positive, while early viraemia clearance (TW12) improved antiviral responses. The cross-over experiment revealed that changes in DC, rather than CD4(+)T cells have a major role for enhanced anti-HCV responses.
对接受聚乙二醇干扰素α2b/利巴韦林治疗的慢性丙型肝炎患者的单核细胞来源的树突状细胞(MDDC)进行血浆和细胞丙型肝炎病毒(HCV)RNA及核心抗原检测。在基线和治疗第12周(TW12)时测量树突状细胞的同种异体刺激能力、HCV特异性T细胞反应性及白细胞介素-12的产生。利用在基线和TW12时获得的树突状细胞和自体CD4(+)T细胞,我们进行了交叉实验,以确定树突状细胞和/或T细胞对HCV免疫反应受损的相对作用。HCV RNA和HCV核心血浆水平对树突状细胞表型和同种异体刺激能力有影响。相比之下,尽管在一些患者的树突状细胞中可检测到HCV基因组/核心蛋白,但对树突状细胞功能没有影响。在TW12时仍为HCV RNA阳性的患者,其抗病毒免疫力没有改善,而早期病毒血症清除(TW12)可改善抗病毒反应。交叉实验表明,树突状细胞的变化而非CD4(+)T细胞的变化在增强抗HCV反应中起主要作用。