The Journal of infectious diseases 2017 05 11() doi 10.1093/infdis/jix223
Increased mortality and morbidity occurs in human immunodeficiency virus (HIV)-infected patients who fail to increase CD4+ T cell counts despite achieving viral suppression with antiretroviral therapy (ART). Here we identified an underlying mechanism. Significantly elevated plasma levels of anti-CD4 IgGs were found in HIV+ immunologic non-responders (CD4+ T cell counts ≤ 350 cells/μl) compared to HIV+ immunologic responders (CD4+ T cell counts ≥ 500 cells/μl) and healthy controls. Higher plasma level of anti-CD4 IgG correlated with blunted CD4+ T cell recovery. Furthermore, purified anti-CD4 IgGs from HIV+ immunologic non-responders induced NK cell-dependent CD4+ T cell cytolysis and apoptosis through antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro. We also found that anti-CD4 IgG-mediated ADCC exerts greater apoptosis on naive relative to memory CD4+ T cells. Consistently, increased frequencies of CD107a+ NK cells and profound decreases of naive CD4+ T cells were observed in immunologic non-responders compared to responders and healthy controls ex vivo. These data indicate that autoreactive anti-CD4 IgGs may play an important role in the blunted CD4+ T cell reconstitution despite effective ART.