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Characterization of antibody-dependent cellular cytotoxicity induced by the plasma from persons living with HIV-1 based on target cells with or without CD4 molecules
Microbes and Infection ( IF 5.8 ) Pub Date : 2021-03-09 , DOI: 10.1016/j.micinf.2021.104805
Yibo Ding 1 , Desheng Kong 2 , Dan Li 1 , Yuanyuan Zhang 1 , Kunxue Hong 1 , Hua Liang 1 , Liying Ma 1
Affiliation  

Antibody-dependent cellular cytotoxicity (ADCC) is essential for reducing the reservoir of latent virus in persons living with HIV-1 (PLWH). This study evaluated the plasma's ADCC activity from treatment-naïve PLWH based on target cells with or without CD4 molecules. We found that the distribution of plasma activities to mediate ADCC is different between 8E5 cells (CD4-) and NL4-3-infected CEM.NKR.CCR5 cells (CD4+). There was no correlation between the IgG-binding ability and ADCC activity. The binding ability of the 8E5 cells (2.2%) to A32 antibody was significantly lower than that of CEM.NKR.CCR5 cells (69.3%). After incubating the 8E5 cells with CD4-mimetic compound, it did not increase the binding ability with the A32 antibody. After incubation with CD4+ T cells, the binding ability of the 8E5 cells for the A32 antibody increased significantly, which implies that the conformation of the Env protein open and expose the CD4-induced epitopes. The effect of the ADCC in plasma directly applied to 8E5 cells was positively correlated with that of the NL4-3-infected CEM.NKR.CCR5 cells. In conclusion, ADCC induction in plasma was general in the treatment-naïve PLWH. The ADCC activity levels differed when target cells with or without CD4 molecules were evaluated; When designing experiments on ADCC, full consideration should be given to this immune phenomenon.



中文翻译:

基于有或没有 CD4 分子的靶细胞,表征由 HIV-1 感染者的血浆诱导的抗体依赖性细胞毒性

抗体依赖性细胞毒性 (ADCC) 对于减少 HIV-1 (PLWH) 感染者的潜伏病毒库至关重要。该研究基于有或没有 CD4 分子的靶细胞评估了未经治疗的 PLWH 的血浆 ADCC 活性。我们发现,在 8E5 细胞 (CD4-) 和 NL4-3 感染的 CEM.NKR.CCR5 细胞 (CD4+) 之间,介导 ADCC 的血浆活性分布是不同的。IgG结合能力和ADCC活性之间没有相关性。8E5细胞(2.2%)与A32抗体的结合能力明显低于CEM.NKR.CCR5细胞(69.3%)。将 8E5 细胞与 CD4 模拟化合物一起孵育后,它与 A32 抗体的结合能力没有增加。与 CD4+ T 细胞孵育后,8E5 细胞对 A32 抗体的结合能力显着增加,这意味着 Env 蛋白的构象打开并暴露了 CD4 诱导的表位。直接应用于 8E5 细胞的血浆中 ADCC 的作用与 NL4-3 感染的 CEM.NKR.CCR5 细胞的作用呈正相关。总之,在未经治疗的 PLWH 中,血浆中的 ADCC 诱导是普遍的。当评估有或没有 CD4 分子的靶细胞时,ADCC 活性水平不同;在ADCC上设计实验时,应充分考虑这种免疫现象。在未经治疗的 PLWH 中,血浆中的 ADCC 诱导是普遍的。当评估有或没有 CD4 分子的靶细胞时,ADCC 活性水平不同;在ADCC上设计实验时,应充分考虑这种免疫现象。在未经治疗的 PLWH 中,血浆中的 ADCC 诱导是普遍的。当评估有或没有 CD4 分子的靶细胞时,ADCC 活性水平不同;在ADCC上设计实验时,应充分考虑这种免疫现象。

更新日期:2021-03-09
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