Center for AIDS Research, Kumamoto University, Japan.
Biochem Biophys Res Commun. 2010 Mar 5;393(2):331-7. doi: 10.1016/j.bbrc.2010.02.008. Epub 2010 Feb 6.
Impaired activity of NK (natural killer) cells has been proposed as a mechanism contributing to viral persistence and chronic infection in hepatitis C (HCV) infection. We aimed to assess the impact of HCV infection on NK cells regarding frequency, subset distribution, and cytotoxic and cytokine secretion functions, as well as IFN-alpha and ribavirin therapeutic effects on NK cells. Significant reduction of total NK frequency and the CD56(dim)16(+) subset was observed in chronic HCV patients. IFN-gamma expression upon stimulation with K562 was severely suppressed but cytotoxicity measured by CD107a expression was maintained. These adverse effects were reversed after treatment with pegylated IFN-alpha and ribavirin; however, these skewed functions were not recovered in treatment-resistant patients. Thus, HCV chronic infection severely affects NK functions, except for cytotoxicity. Altered NK cell frequency and cytokine secretion by HCV infection may contribute to impaired cellular immune response and virus persistence.
NK（自然杀伤）细胞活性受损被认为是导致丙型肝炎病毒（HCV）感染持续和慢性感染的机制之一。我们旨在评估 HCV 感染对 NK 细胞频率、亚群分布、细胞毒性和细胞因子分泌功能的影响，以及 IFN-α和利巴韦林对 NK 细胞的治疗作用。慢性 HCV 患者 NK 细胞总数和 CD56(dim)16(+)亚群显著减少。用 K562 刺激后 IFN-γ的表达受到严重抑制，但通过 CD107a 表达测量的细胞毒性保持不变。用聚乙二醇化 IFN-α和利巴韦林治疗后，这些不良反应得到逆转；然而，在治疗抵抗的患者中，这些偏倚的功能没有恢复。因此，HCV 慢性感染严重影响 NK 功能，除了细胞毒性。HCV 感染导致的 NK 细胞频率和细胞因子分泌改变可能导致细胞免疫应答受损和病毒持续存在。
