Chang Li-Ling, Cheng Pin-Nan, Chen Jiann-Shiuh, Young Kung-Chia
Institute of Molecular Medicine, Medical College, National Cheng Kung University, Tainan 701, Taiwan, ROC.
Antiviral Res. 2007 Jul;75(1):43-51. doi: 10.1016/j.antiviral.2006.11.009. Epub 2006 Dec 14.
The lymphocytic CD81 molecule, capable of modulating type-1/-2 T-helper responses and serving as a putative receptor for hepatitis C virus (HCV), might influence the outcome of anti-HCV treatment. This study characterized the interferon-alpha-induced alteration of lymphocytic CD81. The CD81 levels in healthy subjects and naïve chronic HCV patients were compared, with the results showing that the two groups had comparable surface CD81 levels for total peripheral blood lymphocytes, subpopulation-B, -T, and -NK cells. In vitro interferon-alpha treatment could suppress the CD81 expression from both groups. Subsequently, we compared the in vitro interferon-alpha modulatory effects on lymphocytic CD81 from patients having received anti-HCV therapy with either sustained virological response (SVR) or without SVR. There was a significant down-regulation of the B-cell's CD81 only in the SVR group. The CD81 modulation was further investigated using Daudi lymphoid cell line, showing declined surface CD81 levels following treatment with interferon-alpha, interferon-beta or polyI:C. Thus, interferons could directly decrease CD81 expression. The interferon-alpha effect could be restored by 2-aminopurine, suggesting that double-stranded RNA activated kinase might be involved in the suppression of CD81. In conclusion, CD81 down-regulation is a primary host response to interferon-alpha-based therapy and an immunophenotype associated with anti-HCV SVR.
淋巴细胞CD81分子能够调节1型/2型辅助性T细胞反应，并作为丙型肝炎病毒（HCV）的假定受体，可能会影响抗HCV治疗的结果。本研究对干扰素α诱导的淋巴细胞CD81变化进行了表征。比较了健康受试者和初治慢性HCV患者的CD81水平，结果显示两组外周血淋巴细胞、B细胞亚群、T细胞亚群和NK细胞亚群的表面CD81水平相当。体外干扰素α治疗可抑制两组的CD81表达。随后，我们比较了干扰素α对接受抗HCV治疗且获得持续病毒学应答（SVR）或未获得SVR的患者淋巴细胞CD81的体外调节作用。仅在SVR组中，B细胞的CD81有显著下调。使用Daudi淋巴瘤细胞系进一步研究了CD81的调节作用，结果显示用干扰素α、干扰素β或聚肌胞苷酸（polyI:C）处理后，表面CD81水平下降。因此，干扰素可直接降低CD81表达。2-氨基嘌呤可恢复干扰素α的作用，提示双链RNA激活激酶可能参与了对CD81的抑制。总之，CD81下调是基于干扰素α治疗的主要宿主反应，也是与抗HCV SVR相关的免疫表型。
