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

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.