Department of Microbiology and Infectious Disease, Royal Perth Hospital, Perth, Western Australia, Australia.
J Med Virol. 2010 Apr;82(4):568-74. doi: 10.1002/jmv.21742.
Natural killer (NK) cells are implicated in the regulation of a protective immune response in patients chronically infected with hepatitis C virus (HCV), but effects of interferon-alpha/ribavirin therapy on NK cell subsets and the consequences of viral clearance during therapy remain unclear. Samples were collected from chronically infected patients (n = 34) at baseline and from a subset after 3-10 months on pegylated interferon-alpha and ribavirin therapy (n = 19). NK cells present in cryopreserved PBMC were characterized by flow cytometry. Before therapy, the frequency of CD3-CD56+ NK cells was lower in patients than uninfected controls. Therapy increased proportions of CD56(bright) NK cells. Frequencies of CD56(dim) NK cells declined slightly while perforin and CD16 expression on CD56(dim) NK cells decreased compared to baseline samples. Evaluation of NK cell subsets at baseline did not identify patients able to achieve sustained virological response following therapy. However, therapy may promote the expansion of NK cells able to produce interferon-gamma, while minimizing cytotoxicity to limit liver damage.
自然杀伤 (NK) 细胞被认为参与了慢性丙型肝炎病毒 (HCV) 感染患者的保护性免疫反应的调节,但干扰素-α/利巴韦林治疗对 NK 细胞亚群的影响以及治疗期间病毒清除的后果仍不清楚。本研究从慢性感染患者(n = 34)在基线时和接受聚乙二醇干扰素-α和利巴韦林治疗 3-10 个月后的亚组(n = 19)中采集样本。通过流式细胞术对冷冻保存的 PBMC 中的 NK 细胞进行了特征分析。在治疗前,与未感染对照相比,患者中 CD3-CD56+ NK 细胞的频率较低。治疗增加了 CD56(bright) NK 细胞的比例。与基线样本相比,CD56(dim) NK 细胞的频率略有下降,而 CD56(dim) NK 细胞上的穿孔素和 CD16 表达减少。在基线时评估 NK 细胞亚群不能确定哪些患者在治疗后能够实现持续病毒学应答。然而,治疗可能会促进产生干扰素-γ的 NK 细胞的扩增,同时最大限度地减少细胞毒性以限制肝损伤。