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慢性淋巴细胞白血病淋巴细胞上隐匿性自然杀伤(NK)细胞识别位点的揭示。

Unmasking of cryptic natural killer (NK) cell recognition sites on chronic lymphocytic leukemia lymphocytes.

作者信息

Spitz D L, Zucker-Franklin D, Nabi Z F

机构信息

Department of Medicine, New York University Medical Center, New York 10016.

出版信息

Am J Hematol. 1988 Jul;28(3):155-61. doi: 10.1002/ajh.2830280305.

DOI:10.1002/ajh.2830280305
PMID:3136646
Abstract

The sensitivity of chronic lymphocytic leukemia (CLL) lymphocytes to attack by natural killer (NK) cells has remained questionable. To clarify this issue, freshly isolated lymphocytes of 37 patients with B-CLL, five with WDLL and two with HCL, were tested with a standard cytotoxicity assay with NK cells from normal donors. All these targets were resistant to cytolysis by the effectors. Freeze-fracture analysis of CLL cell plasma membranes revealed that they have a larger number of intramembranous particles (IMP) associated with the external leaflet (E-face) than have normal lymphocytes. Unlike other neoplastic cells, exposure of CLL lymphocytes to phorbol esters or treatment with neuraminidase did not render them vulnerable to attack by NK cells, nor did 5 days of culture have an effect. Incubation of CLL lymphocytes with anti-Ig-mu (24-72 hr) or with 0.1% pepsin (15 min) resulted in 15% and 27% cytolysis, respectively. B-lymphocytes from the blood of healthy donors were not killed when treated similarly: These data establish that freshly isolated B-CLL lymphocytes are resistant to NK cytolysis but that in contrast to normal B-cells, they possess cryptic NK-recognition structures, which may be uncovered by surface modulation.

摘要

慢性淋巴细胞白血病(CLL)淋巴细胞对自然杀伤(NK)细胞攻击的敏感性一直存在疑问。为了阐明这个问题,我们用来自正常供体的NK细胞,通过标准细胞毒性试验对37例B-CLL患者、5例WDLL患者和2例HCL患者的新鲜分离淋巴细胞进行了检测。所有这些靶细胞对效应细胞的细胞溶解均有抗性。对CLL细胞质膜的冷冻断裂分析显示,与正常淋巴细胞相比,它们与外小叶(E面)相关的膜内颗粒(IMP)数量更多。与其他肿瘤细胞不同,CLL淋巴细胞暴露于佛波酯或用神经氨酸酶处理后,并不会使其易于受到NK细胞的攻击,培养5天也没有效果。将CLL淋巴细胞与抗Ig-μ(24 - 72小时)或0.1%胃蛋白酶(15分钟)孵育,分别导致15%和27%的细胞溶解。健康供体血液中的B淋巴细胞在进行类似处理时不会被杀死:这些数据表明,新鲜分离的B-CLL淋巴细胞对NK细胞溶解具有抗性,但与正常B细胞不同的是,它们具有潜在的NK识别结构,这些结构可能通过表面调节而被暴露出来。

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Unmasking of cryptic natural killer (NK) cell recognition sites on chronic lymphocytic leukemia lymphocytes.慢性淋巴细胞白血病淋巴细胞上隐匿性自然杀伤(NK)细胞识别位点的揭示。
Am J Hematol. 1988 Jul;28(3):155-61. doi: 10.1002/ajh.2830280305.
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Cancers (Basel). 2022 Nov 24;14(23):5787. doi: 10.3390/cancers14235787.
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NK Cells in Chronic Lymphocytic Leukemia and Their Therapeutic Implications.自然杀伤细胞在慢性淋巴细胞白血病中的作用及其治疗意义。
Int J Mol Sci. 2021 Jun 22;22(13):6665. doi: 10.3390/ijms22136665.
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Immune Dysfunctions and Immune-Based Therapeutic Interventions in Chronic Lymphocytic Leukemia.慢性淋巴细胞白血病中的免疫功能紊乱及基于免疫的治疗干预。
Front Immunol. 2020 Nov 18;11:594556. doi: 10.3389/fimmu.2020.594556. eCollection 2020.
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Neutralization of (NK-cell-derived) B-cell activating factor by Belimumab restores sensitivity of chronic lymphoid leukemia cells to direct and Rituximab-induced NK lysis.贝利尤单抗中和(NK 细胞来源的)B 细胞激活因子可恢复慢性淋巴细胞白血病细胞对直接和利妥昔单抗诱导的 NK 细胞溶解的敏感性。
Leukemia. 2015 Aug;29(8):1676-83. doi: 10.1038/leu.2015.50. Epub 2015 Feb 24.
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Primary B-CLL resistance to NK cell cytotoxicity can be overcome in vitro and in vivo by priming NK cells and monoclonal antibody therapy.原发性 B-CLL 对 NK 细胞细胞毒性的耐药性可以通过激活 NK 细胞和单克隆抗体治疗在体外和体内得到克服。
J Clin Immunol. 2012 Jun;32(3):632-46. doi: 10.1007/s10875-011-9624-5. Epub 2012 Feb 9.
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Biology of natural killer cells.自然杀伤细胞生物学
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