BACKGROUND Multiple immune evasion strategies by which HCV establishes chronic infection have been proposed, including manipulation of cytokine responses. Prior infection with HIV increases the likelihood of chronic HCV infection and accelerates development of HCV-related morbidity. Therefore, we investigated in vitro cytokine responses to HCV structural and non-structural proteins in peripheral blood mononuclear cells (PBMC) from uninfected, HIV-infected, HCV-infected and HIV/HCV-coinfected individuals. RESULTS Intracellular flow cytometry was used to assess IL-2, IL-10, IL-12, and IFN-gamma production by freshly isolated PBMC incubated for 16 hours with recombinant HCV core, non-structural protein 3 (NS3), and NS4 proteins. Anti-HCV cellular responses were assessed in HIV/HCV-coinfected individuals by 3H-thymidine proliferation assay. Exposure to HCV antigens increased IL-10 production by PBMC, especially in uninfected and HIV-monoinfected individuals. This IL-10 response was attenuated in chronic HCV infection even with HCV/HIV-coinfection. The cells producing IL-10 in response to HCV proteins in vitro matched a PBMC subset recently shown to constitutively produce IL-10 in vivo. This subset was found at similar frequencies in uninfected, HIV-infected, HCV-infected and HIV/HCV-coinfected individuals before exposure to HCV proteins. HCV-specific T cell proliferation was detectable in only one HIV/HCV-coinfected individual who demonstrated no HCV-induced IL-10 response. CONCLUSION This pattern suggests that selective induction of IL-10 in uninfected individuals and especially in HIV-monoinfected individuals plays a role in establishing chronic HCV infection and conversely, that attenuation of this response, once chronic infection is established, favours development of hepatic immunopathology.

中文翻译：

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来自人类免疫缺陷病毒单一感染者的外周血单核细胞对丙型肝炎病毒蛋白的反应增强了 IL-10 的产生。

背景已经提出了HCV建立慢性感染的多种免疫逃避策略，包括操纵细胞因子反应。先前感染 HIV 会增加慢性 HCV 感染的可能性并加速 HCV 相关发病率的发展。因此，我们研究了来自未感染、HIV 感染、HCV 感染和 HIV/HCV 合并感染个体的外​​周血单核细胞 (PBMC) 中 HCV 结构和非结构蛋白的体外细胞因子反应。结果 细胞内流式细胞术用于评估新鲜分离的 PBMC 与重组 HCV 核心、非结构蛋白 3 (NS3) 和 NS4 蛋白孵育 16 小时后产生的 IL-2、IL-10、IL-12 和 IFN-γ . 通过 3 H-胸苷增殖测定在 HIV/HCV 共感染个体中评估抗 HCV 细胞反应。接触 HCV 抗原会增加 PBMC 产生的 IL-10，尤其是在未感染和 HIV 单一感染的个体中。这种 IL-10 反应在慢性 HCV 感染中减弱，即使是 HCV/HIV 合并感染。体外响应 HCV 蛋白产生 IL-10 的细胞与最近显示在体内组成性产生 IL-10 的 PBMC 子集相匹配。在暴露于 HCV 蛋白之前，在未感染、HIV 感染、HCV 感染和 HIV/HCV 合并感染的个体中发现该子集的频率相似。仅在一名未表现出 HCV 诱导的 IL-10 反应的 HIV/HCV 共感染个体中可检测到 HCV 特异性 T 细胞增殖。结论 这种模式表明，在未感染的个体中，尤其是在单纯感染 HIV 的个体中选择性诱导 IL-10 在建立慢性 HCV 感染中起作用，相反，