Impaired ability of interferon-alpha-primed dendritic cells to stimulate Th1-type CD4 T-cell response in chronic hepatitis C virus infection
Impaired ability of interferon-alpha-primed dendritic cells to stimulate Th1-type CD4 T-cell response in chronic hepatitis C virus infection
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DOI：
10.1111/j.1365-2893.2006.00814.x
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发表时间：
2007-06-01
影响因子：
2.5
通讯作者：
Hayashi, N.
中科院分区：
文献类型：
--
作者：
Miyatake, H.;Kanto, T.;Hayashi, N.
在干扰素-α（IFN-α）/利巴韦林联合治疗慢性丙型肝炎（CHC）中，增强的辅助性T细胞1（Th 1）应答对于根除丙型肝炎病毒（HCV）至关重要。我们的目的是阐明IFN-α或IFN-α/利巴韦林在丙型肝炎病毒感染中树突状细胞（DC）诱导Th 1应答能力中的作用。我们从20名CHC患者和15名正常受试者中产生单核细胞衍生的DC，由粒细胞-巨噬细胞集落刺激因子和白细胞介素4（IL-4）驱动，无IFN-α（GM/4-DC），IFN-α（IFN-DC），利巴韦林（R-DC）或IFN-α/利巴韦林（IFN/R-DC），并比较各组之间的表型和功能。我们还比较了14例CHC患者在IFN-α/利巴韦林治疗24周后获得持续病毒学应答（SVR）和未获得持续病毒学应答（非SVR）的患者。与GM/4-DC相比，IFN-DC显示出更高的CD 86表达，但分泌IL-10的能力较低，并且更有效地引发CD 4（+）T细胞分泌IFN-γ和IL-2。这种差异在健康受试者中比在CHC患者中更显著。利巴韦林单独使用或与IFN-α联合使用对体外DC表型和功能均无累加效应。然而，在SVR患者中，IFN/R-DC引发T细胞分泌IFN-γ和IL-2的能力分别高于非SVR组中IFN/R-DC和IFN/R-DC的那些。总之，来自CHC患者的DC响应IFN-α驱动Th 1的能力受损。这种DC损伤在体外通过加入利巴韦林而在通过联合治疗清除HCV的部分患者中恢复。
In interferon-alpha (IFN-alpha)/ribavirin combination therapy for chronic hepatitis C (CHC), an enhanced T helper 1 (Th1) response is essential for the eradication of hepatitis C virus (HCV). We aimed to elucidate the role of IFN-alpha or IFN-alpha/ribavirin in dendritic cell (DC) ability to induce Th1 response in HCV infection. We generated monocyte-derived DC from 20 CHC patients and 15 normal subjects driven by granulocyte-macrophage colony-stimulating factor and interleukin 4 (IL-4) without IFN-alpha (GM/4-DC), with IFN-alpha (IFN-DC), with ribavirin (R-DC) or with IFN-alpha/ribavirin (IFN/R-DC) and compared their phenotypes and functions between the groups. We also compared them in 14 CHC patients between who subsequently attained sustained virological response (SVR) and who did not (non-SVR) by 24 weeks of IFN-alpha/ribavirin therapy. Compared with GM/4-DC, IFN-DC displayed higher CD86 expression, but lesser ability to secrete IL-10 and were more potent to prime CD4(+) T cells to secrete IFN-gamma and IL-2. Such differences were more significant in healthy subjects than in CHC patients. No additive effect of ribavirin was observed in DC phenotypes and functions in vitro either which was used alone or in combined with IFN-alpha. However, in the SVR patients, an ability of IFN/R-DC to prime T cells to secrete IFN-gamma and IL-2 was higher than those of IFN-DC and those of IFN/R-DC in the non-SVR group, respectively. In conclusion, DC from CHC patients are impaired in the ability to drive Th1 in response to IFN-alpha. Such DC impairment is restored in vitro by the addition of ribavirin in not all but some patients who cleared HCV by the combination therapy.