Anti-CD4 autoantibodies in immunological nonresponder people with HIV: cause of CD4(+) T-cell depletion?

Objective: Weaimed to evaluate the anti-CD4 IgG role in the poor immune recovery of immunological nonresponder people with HIV (INR). Design: INR display low CD4(+) T-cell increase despite long-term undetectable viremia. Among other factors, autologous anti-CD4 IgG-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells has been proposed to cause CD4(+) T-cell depletion. Methods: Plasma anti-CD4 IgG levels were quantified and purified by chromatography columns for the subsequent use in a coculture of CD4(+) T and NK cells. We analyzed NK cell degranulation markers (CD107a, perforin and granzyme B) and IFN-gamma release, and CD4(+) T-cell death. Binding affinity of anti-CD4 IgG for CD4(+) T cells was also assessed. Results: A total of 168 individuals were enrolled (INR, 56; immunological responders, 40; treatment-naive, 39; and healthy controls, 33). The highest anti-CD4 IgG levels were found in treatment-naive people with HIV (PWH), followed by participants on treatment. There were no correlations between anti-CD4 IgG levels and CD4(+) T-cell counts. In a 15-participant subgroup (naive, immunological responders, and INR), anti-CD4 IgG induced a slight NK-cell expression of degranulation markers and IFN-gamma; however, the percentage of CD4(+) T-cell death was negligible. Consistently, no significant changes in NK cell polyfunctionality were observed. In addition, purified anti-CD4 IgG showed scarce binding affinity for CD4(+) T cells. These results were similar in all analyzed participant groups. Conclusion: Our results suggest that autologous anti-CD4 IgG neither trigger CD4(+) T-cell death by ADCC nor are responsible for CD4(+) lymphocyte depletion in INR. Video abstract: http://links.lww.com/QAD/C518. Copyright (C) 2022 Wolters Kluwer Health, Inc. All rights reserved.