Natural killer cells in hepatitis C virus infection: from innate immunity to adaptive immunity.
Natural killer cells in hepatitis C virus infection: from innate immunity to adaptive immunity.
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DOI：
10.1016/s1542-3565(05)00702-0
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发表时间：
2005-10-01
期刊：
影响因子：
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通讯作者：
Hayashi, Norio
中科院分区：
文献类型：
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作者：
Takehara, Tetsuo;Hayashi, Norio
自然杀伤细胞（NK）是一种特殊的淋巴细胞，通过杀死病原体感染细胞和转化细胞的能力提供第一道防线。NK细胞的功能受抑制和激活信号的微妙平衡调节，这些信号由多种细胞表面受体介导。我们最近发现，慢性丙型肝炎患者NK细胞中抑制受体CD94/NKG2A的表达上调。NKG2A的配体HLA-E在所有人肝癌细胞系以及未转化的肝细胞中表达，但在K562细胞中不表达，K562细胞是典型的NK敏感靶点。从慢性丙型肝炎患者体内分离的NK细胞（HCV-NK）对肝癌细胞的杀伤能力和对肝癌细胞产生干扰素- γ的能力低于健康供体，而NK细胞对K562细胞的反应性没有显著差异。值得注意的是，单核细胞来源的树突状细胞的成熟和激活在HCV-NK和肝癌细胞存在下被负调节，在HCV-NK和肝癌细胞共培养期间，通过添加抗nkg2a抗体，树突状细胞的成熟和激活被恢复。研究表明，树突状细胞通过toll样受体监测病原体相关分子模式来识别来自微生物的危险信号。我们的研究结果揭示了NK受体作为一个重要的界面，将危险信号从异常细胞传递到免疫系统。CD94/NKG2A的异常表达可能对慢性丙型肝炎患者对hcv感染或转化细胞的先天抵抗和随后的适应性免疫产生负面影响。
Natural killer (NK) cells are specialized lymphocytes that provide a first line of defense through their ability to kill pathogen-infected cells and transformed cells. The function of NK cells is regulated by a fine balance of inhibitory and activating signals, which are mediated by a diverse array of cell-surface receptors. We recently found that expression of the inhibitory receptor CD94/NKG2A is up-regulated on NK cells in patients with chronic hepatitis C. HLA-E, a ligand for NKG2A, was expressed in all human hepatoma cell lines tested as well as in nontransformed hepatocytes, but not in K562 cells, a classic NK-sensitive target. NK cells isolated from patients with chronic hepatitis C (HCV-NK) were less capable of killing hepatoma cells and of producing interferon-gamma in response to hepatoma cells than those from healthy donors, whereas there was no significant difference in NK responsiveness toward K562 cells. Of note is the finding that maturation and activation of monocyte-derived dendritic cells were negatively modulated in the presence of HCV-NK and hepatoma cells, which were restored by the addition of anti-NKG2A antibody during the coculture of HCV-NK and hepatoma cells. Research revealed that dendritic cells recognize danger signals from microorganisms by monitoring pathogen-associated molecular patterns via Toll-like receptors. Our findings have shed light on NK receptors as an important interface that transmits danger signals from abnormal cells to immune systems. Aberrant expression of CD94/NKG2A should have negative impact on innate resistance and subsequent adaptive immunity toward HCV-infected or transformed cells in chronic hepatitis C.