Corrigendum: CD16 is indispensable for antibody-dependent cellular cytotoxicity by human monocytes.
Corrigendum: CD16 is indispensable for antibody-dependent cellular cytotoxicity by human monocytes.
复制标题
DOI：
10.1038/srep46202
复制
发表时间：
2017-04-07
影响因子：
4.6
通讯作者：
Wong SC
中科院分区：
文献类型：
--
作者：
Yeap WH;Wong KL;Shimasaki N;Teo EC;Quek JK;Yong HX;Diong CP;Bertoletti A;Linn YC;Wong SC
抗体依赖性细胞毒性（ADCC）是由表达表面Fcγ受体（Fcγ R）的免疫细胞对抗体包被的细胞（如病毒感染或转化细胞）产生的。CD 16（FcγRIIIA）是NK细胞ADCC所必需的，也由人血液单核细胞亚群表达。我们发现，表达人CD 16 −的单核细胞具有广谱ADCC能力，在特异性抗体存在下可以杀死癌细胞系、原代白血病细胞和B型肝炎病毒感染的细胞。通过与靶细胞结合的抗体结合单核细胞上的CD 16激活β2-整合素并诱导TNFα分泌。反过来，这会诱导靶细胞上的TNFR表达，使它们容易受到TNFα介导的细胞死亡的影响。用TLR激动剂、DAMP或细胞因子如IFNγ治疗进一步增强ADCC。缺乏CD 16的单核细胞不发挥ADCC，但获得此属性后，通过细胞因子刺激或瞬时转染诱导CD 16表达。值得注意的是，来自白血病患者的CD 16+单核细胞也发挥了有效的ADCC。因此，CD 16+单核细胞是ADCC的重要效应子，这表明在癌症和感染性疾病的细胞疗法的背景下进一步开发了该特性。
Antibody-dependent cellular cytotoxicity (ADCC) is exerted by immune cells expressing surface Fcγ receptors (FcγRs) against cells coated with antibody, such as virus-infected or transformed cells. CD16, the FcγRIIIA, is essential for ADCC by NK cells, and is also expressed by a subset of human blood monocytes. We found that human CD16− expressing monocytes have a broad spectrum of ADCC capacities and can kill cancer cell lines, primary leukemic cells and hepatitis B virus-infected cells in the presence of specific antibodies. Engagement of CD16 on monocytes by antibody bound to target cells activated β2-integrins and induced TNFα secretion. In turn, this induced TNFR expression on the target cells, making them susceptible to TNFα-mediated cell death. Treatment with TLR agonists, DAMPs or cytokines, such as IFNγ, further enhanced ADCC. Monocytes lacking CD16 did not exert ADCC but acquired this property after CD16 expression was induced by either cytokine stimulation or transient transfection. Notably, CD16+ monocytes from patients with leukemia also exerted potent ADCC. Hence, CD16+ monocytes are important effectors of ADCC, suggesting further developments of this property in the context of cellular therapies for cancer and infectious diseases.