Increased natural cytotoxicity receptor expression and relevant IL-10 production in NK cells from chronically infected viremic HCV patients
Increased natural cytotoxicity receptor expression and relevant IL-10 production in NK cells from chronically infected viremic HCV patients
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DOI：
10.1002/eji.200635989
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发表时间：
2007-02-01
影响因子：
5.4
通讯作者：
Moretta, Lorenzo
中科院分区：
文献类型：
--
作者：
De Maria, Andrea;Fogli, Manuela;Moretta, Lorenzo
丙型肝炎病毒（HCV）容易在大多数免疫功能正常的成年人中建立高水平的终身持续感染，HCV特异性CD 8（+）CTL无法清除病毒复制。病毒诱导的先天性免疫应答条件化是可能导致病毒特异性CD 8 + CTL应答受损的可能机制。在这里，我们分析了在慢性病毒血症HCV感染期间，NK细胞受体表达和功能的触发是否受到影响。对纯化的静息外周NK细胞的流式细胞术分析显示没有NK细胞活化的证据，而对天然细胞毒性受体（NCR）的分析显示来自HCV感染患者的NK细胞具有NKp 30和NKp 46的选择性增加的表达。NK细胞对除HepG 2肝癌细胞外的所有靶细胞具有相应的保守细胞毒活性。来自HCV患者的新鲜分离的NK细胞在细胞介导的触发后显示出显著的IL-10产生和正常浓度的IFN-γ。因此，一旦NK细胞定位于肝脏中，HCV感染期间NKp 30的表达增加以及IL-10产生增加可能有助于NK-DC串扰，导致随后的适应性免疫应答的偏斜和缺乏病毒控制。
Hepatitis C virus (HCV) readily establishes high-level lifelong persistent infection in the majority of immunocompetent adults with failure of HCV-specific CD8(+) CTL to clear viral replication. Virus-induced conditioning of innate immune responses is a possible mechanism that may contribute to the impairment of virus-specific CD8+ CTL responses. Here, we analyzed whether triggering of NK cell receptor expression and function is affected during chronic viremic HCV infection. Flow cytometric analysis of purified resting peripheral NK cells showed no evidence of NK cell activation, while analysis of natural cytotoxicity receptors (NCR) showed that NK cells from HCV-infected patients had selective increased expression of NKp30 and NKp46. NK cells had corresponding conserved cytotoxic activity against all targets with the exception of HepG2 hepatoma cells. Freshly separated NK cells from HCV patients showed significant production of IL-10 and normal concentrations of IFN-gamma upon cell-mediated triggering. Thus, increased expression of NKp30 during HCV infection with increased IL-10 production could contribute, once NK cells localize in the liver, to a NK-DC crosstalk leading to skewing of subsequent adaptive immune responses and lack of virus control.