Identification of NKG2A and NKp80 as specific natural killer cell markers in rhesus and pigtailed monkeys

Identification of NKG2A and NKp80 as specific natural killer cell markers in rhesus and pigtailed monkeys
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DOI:
10.1182/blood-2004-12-4762
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发表时间:
2005-09-01
期刊:
影响因子:
20.3
通讯作者:
Fauci, AS
Fauci, AS
中科院分区:
医学1区
文献类型:
--
作者:
Mavilio, D;Benjamin, J;Fauci, AS

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由于缺乏适当的表型标记物和对NK细胞活性调节的认识不足,对猿猴疾病模型中自然杀伤(NK)细胞的研究受到阻碍。在本研究中,筛选了一组对各种人NK受体具有特异性的单克隆抗体(mAb),用于与恒河猴和猪尾猕猴的NK细胞的交叉反应性。单独使用抗人NKG2A和抗人NKp80 mAb,特别是与抗CD16 mAb联合使用进行流式细胞术分析,可鉴别两个种属中的整个NK细胞群。通常通过对外周血单核细胞(PBMC)进行阴性选择以确定是否存在T细胞、B细胞和单核细胞标志物来鉴定猴中的NK细胞。mAb介导的NKp80连接诱导NK细胞的细胞毒性,而在NKG2A的情况下,它显示出明显的抑制来自猕猴以及来自人的NK细胞对靶细胞的裂解的能力。恒河猴和猪尾猕猴NK细胞中NKG2A和NKp80的这种新的表型和功能表征为分析其先天免疫系统提供了新的方法。
Investigations of natural killer (NK) cells in simian models of disease have been hampered by a lack of appropriate phenotypic markers and by an inadequate understanding of the regulation of NK cell activities. In the present study, a panel of monoclonal antibodies (mAbs) specific for various human NK receptors was screened for cross-reactivity with NK cells from rhesus macaques and pigtailed macaques. Flow cytometric analyses using anti-human NKG2A and anti-human NKp80 mAbs individually, and particularly in combination with anti-CD16 mAb, allowed for the identification of the entire NK cell population in both species. NK cells in monkeys were generally identified by negative selection of peripheral blood mononuclear cells (PBMCs) for the absence of T-cell, B-cell, and monocyte markers. mAb-mediated ligation of NKp8O induced NK cell cytotoxicity, while in the case of NKG2A it displayed a clear capability to inhibit the lysis of target cells by NK cells from macaques, as well as from humans. This new phenotypic and functional characterization of NKG2A and NKp80 in rhesus and pigtailed macaque NK cells provides a new approach in the analysis of their innate immune system.