Analysis of effector cells in human antibody-dependent cellular cytotoxicity with murine monoclonal antibodies.
Analysis of effector cells in human antibody-dependent cellular cytotoxicity with murine monoclonal antibodies.
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使用鼠单克隆抗体分析人抗体依赖性细胞毒性中的效应细胞。
DOI：
10.4049/jimmunol.138.10.3566
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发表时间：
1987
影响因子：
4.4
通讯作者：
R. Reisfeld
中科院分区：
文献类型：
--
作者：
J. Ortaldo;Clive S. Woodhouse;A. Morgan;R. Herberman;D. Cheresh;R. Reisfeld
我们检查了纯化的人大颗粒淋巴细胞、外周单核细胞和 T 细胞利用鼠单克隆抗体介导抗体依赖性细胞毒性 (ADCC) 的能力。我们还评估了用白细胞介素 2 和干扰素预处理细胞以增强 ADCC 活性的效果。 MB3.6 是一种针对 GD3 神经节苷脂的鼠单克隆抗体，可诱导高水平的 ADCC。这种 ADCC 主要（即使不是完全）由人类杀伤细胞（大颗粒淋巴细胞）介导，而其他效应细胞群在 6 小时或 18 小时测定中没有表现出显着的细胞毒活性。 IgG2a（一种抗黑色素瘤抗体 9.2.27）对大多数正常供体或黑色素瘤患者产生低 ADCC 或无 ADCC。 IL 2 是 ADCC 活性的非常有效的增强剂。干扰素α也有效，而干扰素γ并不增强反应性而是抑制反应性。我们针对结肠癌细胞测试了大量不同同种型的抗体，发现 γ-3 同种型抗体比 IgG1 或 IgG2 抗体更频繁地产生 ADCC，并产生更高水平的细胞毒活性。看来多种参数可以影响 ADCC 反应，包括效应细胞的类型及其激活水平、抗体的同种型以及靶细胞系的特性（例如其对裂解的敏感性）。
We examined purified human large granular lymphocytes, peripheral monocytes, and T cells for their ability to mediate antibody-dependent cellular cytotoxicity (ADCC) with murine monoclonal antibodies. We also evaluated the effects of pretreatment of cells with interleukin 2 and interferon to augment ADCC activity. MB3.6, a murine monoclonal antibody directed against the GD3 ganglioside, induced high levels of ADCC. This ADCC was mediated predominantly, if not completely, by human killer cells (large granular lymphocytes) whereas other effector cell populations demonstrated no significant cytotoxic activity in 6- or 18-hr assays. The IgG2a an anti-melanoma antibody 9.2.27 generated low or no ADCC with most normal donors or melanoma patients. IL 2 was a very potent booster of ADCC activity. Interferon alpha also was effective, whereas interferon gamma did not augment but rather inhibited reactivity. We tested a large panel of antibodies of various isotype against colon carcinoma cells and found that gamma-3 isotype antibodies more frequently generated ADCC and produced higher levels of cytotoxic activity than did IgG1 or IgG2 antibodies. It appears that a variety of parameters can affect ADCC reactions, including the type of effector cell and its level of activation, the isotype of the antibody, and properties of the target cell line such as its susceptibility to lysis.