HLA class I, NKG2D, and natural cytotoxicity receptors regulate multiple myeloma cell recognition by natural killer cells
HLA class I, NKG2D, and natural cytotoxicity receptors regulate multiple myeloma cell recognition by natural killer cells
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DOI：
10.1182/blood-2004-04-1422
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发表时间：
2005-01-01
期刊：
影响因子：
20.3
通讯作者：
Venuta, S
中科院分区：
文献类型：
--
作者：
Carbone, E;Neri, P;Venuta, S
自然杀伤细胞（INK）在多发性骨髓瘤中的作用尚不完全清楚。在这里，来自不同疾病阶段的骨髓瘤细胞的NK易感性与主要组织相容性复合体（MHC） I类、MHC I类链相关蛋白A （MICA）、MHC I类链相关蛋白B （MICB）和UL16结合蛋白（ULBP）表达有关。早期骨髓瘤骨髓细胞中几乎检测不到MHC I类分子，而晚期胸膜积液来源细胞系显示出强烈的MHC I类表达。相反，骨髓骨髓瘤细胞的MICA水平较高，而胸膜积液骨髓瘤细胞的MICA水平较低或无法测量。这些分子在骨髓和胸腔积液源性细胞上的互易表面表达在mRNA水平上得到证实。骨髓来源的骨髓瘤细胞很容易被NK细胞识别，而胸膜积液来源的细胞系则有抗性。NK对胸腔积液细胞的保护作用依赖于MHC I类。受体阻断实验表明，凝集素样受体家族（NKG2D）的天然细胞毒性受体（NCR）和INK受体成员D是骨髓源性骨髓瘤细胞识别的关键INK激活受体。在离体实验中，患者的自体新鲜NK细胞可识别骨髓源性骨髓瘤细胞。我们的数据支持NK细胞毒性可以雕刻骨髓瘤的假设，并代表了控制其髓内分期的重要免疫效应机制。(C) 2005年由美国血液病学会出版。
The role of natural killer (INK) cells in multiple myeloma is not fully understood. Here, NK susceptibility of myeloma cells derived from distinct disease stages was evaluated in relation to major histocompatibility complex (MHC) class I, MHC class I chain-related protein A (MICA), MHC class I chain-related protein B (MICB), and UL16 binding protein (ULBP) expression. MHC class I molecules were hardly detectable on bone marrow cells of early-stage myeloma, while late-stage pleural effusion-derived cell lines showed a strong MHC class I expression. Conversely, a high MICA level was found on bone marrow myeloma cells, while it was low or not measurable on pleural effusion myeloma cells. The reciprocal surface expression of these molecules on bone marrow-and pleural effusion-derived cell was confirmed at mRNA levels. While bone marrow-derived myeloma cells were readily recognized by NK cells, pleural effusion-derived lines were resistant. NK protection of pleural effusion cells was MHC class I dependent. Receptor blocking experiments demonstrated that natural cytotoxicity receptor (NCR) and INK receptor member D of the lectin-like receptor family (NKG2D) were the key INK activating receptors for bone marrow-derived myeloma cell recognition. In ex vivo experiments patient's autologous fresh NK cells recognized bone marrow-derived myeloma cells. Our data support the hypothesis that NK cell cytotoxicity could sculpture myeloma and represents an important immune effector mechanism in controlling its intramedullary stages. (C) 2005 by The American Society of Hematology.