Benlarbi Mehdi, Richard Jonathan, Clemente Tommaso, Bourassa Catherine, Tolbert William D, Gottumukkala Suneetha, Peet Marc-Messier, Medjahed Halima, Pazgier Marzena, Maldarelli Frank, Castagna Antonella, Durand Madeleine, Finzi Andrés
medRxiv. 2025 Feb 26:2025.02.25.25322882. doi: 10.1101/2025.02.25.25322882.
While antiretroviral therapy efficiently suppresses viral replication, inflammation and immune dysfunction persist in some people living with HIV-1 (PLWH). Soluble gp120 (sgp120) has been detected in PLWH plasma and its presence is linked to immune dysfunction. It was reported that sgp120 binding to CD4 on uninfected bystander CD4 T cells sensitizes them to antibody-dependent cellular-cytotoxicity (ADCC) mediated by non-neutralizing antibodies present in PLWH plasma. Using three independent PLWH cohorts, we observed that non-neutralizing anti-cluster A antibodies are negatively associated with CD4 T cell counts. Anti-CD4BS antibodies blocked the coating of uninfected bystander cells by sgp120, thereby preventing their elimination by ADCC. Supporting a protective role of anti-CD4BS antibodies, PLWH having these antibodies didn't show a negative association between CD4 T cell counts and anti-cluster A. Our results reveal that anti-cluster A antibodies are associated with immune dysfunction in PLWH and anti-CD4BS antibodies might have a beneficial impact in these individuals.
虽然抗逆转录病毒疗法能有效抑制病毒复制，但在一些人类免疫缺陷病毒1型感染者（PLWH）中，炎症和免疫功能障碍仍然存在。在PLWH的血浆中已检测到可溶性gp120（sgp120），其存在与免疫功能障碍有关。据报道，sgp120与未感染的旁观者CD4 T细胞上的CD4结合，会使它们对PLWH血浆中存在的非中和抗体介导的抗体依赖性细胞毒性（ADCC）敏感。通过三个独立的PLWH队列，我们观察到非中和抗A簇抗体与CD4 T细胞计数呈负相关。抗CD4BS抗体可阻止sgp120对未感染旁观者细胞的包被，从而防止其被ADCC清除。支持抗CD4BS抗体具有保护作用的是，具有这些抗体的PLWH在CD4 T细胞计数和抗A簇之间未显示出负相关。我们的结果表明，抗A簇抗体与PLWH的免疫功能障碍有关，而抗CD4BS抗体可能对这些个体有有益影响。
