Chair and Department of Clinical Immunology, University of Medical Sciences, Rokietnicka 5D, 60-806, Poznan, Poland.
Arch Immunol Ther Exp (Warsz). 2011 Dec;59(6):449-55. doi: 10.1007/s00005-011-0145-y. Epub 2011 Oct 5.
Innate immunity appears to play an important role in the pathogenesis of viral hepatitis C. Among various cell subsets of this immunity natural killer (NK) cells raised particular interest. These cells are abundant in liver, possess significant cytotoxic potential and show links with adaptive immunity. They play important role, particularly in the acute phase of viral infections, including hepatitis C. They exhibit various types of receptors, either inhibitory or activating, that are able to react with distinct ligands on infected cells. Homozygosity of some receptors, namely KIR2DL3 reacting with recipient HLA-C1 antigens is a herald of good prognosis in hepatitis C virus (HCV) infection. In the early stage of the latter, both the prevalence and the cytotoxicity of NK cells are increased. Their inhibitory receptors are down regulated whereas activating ones are up regulated. Interferon-γ secreted by NK56(+bright) NK cells has a direct cytotoxic effect on infected hepatocytes. In contrast, in the chronic phase of HCV liver disease both, the prevalence and function of NK cells are impaired. Nevertheless, their cytotoxicity contributes to liver injury. Cells show change in the polarization profile from NK1 to NK2, manifested by secretion of immunosuppressive cytokines. Some HCV peptides are inhibitory for NK cells leading to the reduction of their antiviral activity. The unwanted effects of HCV peptides can be at least partly reversed by the antiviral therapy.
先天免疫似乎在丙型病毒性肝炎的发病机制中起着重要作用。在这种免疫的各种细胞亚群中，自然杀伤 (NK) 细胞引起了特别的兴趣。这些细胞在肝脏中丰富，具有显著的细胞毒性潜力，并与适应性免疫有关。它们在包括丙型肝炎在内的病毒感染的急性期发挥着重要作用。它们表现出各种类型的受体，无论是抑制性的还是激活性的，能够与受感染细胞上的不同配体反应。某些受体（即与受体 HLA-C1 抗原反应的 KIR2DL3）的纯合性是丙型肝炎病毒 (HCV) 感染预后良好的标志。在后者的早期阶段，NK 细胞的患病率和细胞毒性都增加。其抑制性受体下调，而激活受体上调。NK56(+bright)NK 细胞分泌的干扰素-γ对受感染的肝细胞具有直接的细胞毒性作用。相比之下，在丙型肝炎肝病的慢性阶段，NK 细胞的患病率和功能都受损。然而，它们的细胞毒性有助于肝损伤。细胞表现出从 NK1 到 NK2 的极化谱变化，表现为免疫抑制性细胞因子的分泌。一些 HCV 肽对 NK 细胞具有抑制作用，导致其抗病毒活性降低。HCV 肽的不良作用至少可以部分通过抗病毒治疗来逆转。
