Lichterfeld Mathias, Leifeld Ludger, Nischalke Hans Dieter, Rockstroh Jürgen K, Hess Lothar, Sauerbruch Tilman, Spengler Ulrich
Department of General Internal Medicine, Rheinische Friedrich Wilhelms Universität, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany.
J Infect Dis. 2002 Jun 15;185(12):1803-7. doi: 10.1086/340829. Epub 2002 May 20.
T cell recruitment to the infected liver is an essential step for the efficient elimination of hepatitis viruses. The surface expression of CC chemokine receptor (CCR) 1, CCR4, and CCR5 on peripheral blood T lymphocytes and their responsiveness to the chemokines macrophage inflammatory proteins (MIP)-1alpha, MIP-1beta, and RANTES (regulated on activation, normally T cell-expressed and secreted) was analyzed in patients with chronic hepatitis C and hepatitis B infection and compared with healthy subjects. Although CCR4 surface expression was not altered, hepatitis C virus (HCV)-infected patients had lower proportions of CD8 T cells with CCR1 and CCR5 surface expression (P<.05). Migration of CD8 T cells in response to MIP-1alpha, MIP-1beta, and RANTES was significantly reduced in HCV-infected patients (P<.05). Intracellular CCR1 and CCR5 protein and messenger RNA levels in peripheral blood T cells did not indicate reduced chemokine receptor biosynthesis in hepatitis C infection. Thus, chronic hepatitis C, but not hepatitis B, infection alters surface expression of distinct CCRs, resulting in lower CC chemokine responsiveness.
T细胞向受感染肝脏的募集是有效清除肝炎病毒的关键步骤。分析了慢性丙型肝炎和乙型肝炎感染患者外周血T淋巴细胞上CC趋化因子受体（CCR）1、CCR4和CCR5的表面表达及其对趋化因子巨噬细胞炎性蛋白（MIP）-1α、MIP-1β和调节激活正常T细胞表达和分泌因子（RANTES）的反应性，并与健康受试者进行比较。虽然CCR4表面表达未改变，但丙型肝炎病毒（HCV）感染患者中CCR1和CCR5表面表达的CD8 T细胞比例较低（P<0.05）。HCV感染患者中，CD8 T细胞对MIP-1α、MIP-1β和RANTES的迁移显著减少（P<0.05）。外周血T细胞中细胞内CCR1和CCR5蛋白及信使核糖核酸水平表明丙型肝炎感染中趋化因子受体生物合成未减少。因此，慢性丙型肝炎感染而非乙型肝炎感染会改变不同CCR的表面表达，导致对CC趋化因子的反应性降低。
