The effect of plasma auto‐IgGs on CD4+ T cell apoptosis and recovery in HIV‐infected patients under antiretroviral therapy

Autoantibodies binding on CD4+ T cells may mediate CD4+ T cell death, and prevent CD4+ T cell recovery in aviremic HIV‐infected patients under ART. Although effective antiretroviral therapy (ART) suppresses HIV viral replication, prevents AIDS‐related complications, and prolongs life, a proportion of patients fails to restore the patients’ CD4+ T cell number to the level of healthy individuals. Increased mortality and morbidity have been observed in these patients. In the current study, we have investigated the role of auto‐IgGs in CD4+ T cell apoptosis and recovery in a cross‐sectional study. All HIV+ subjects were on viral‐suppressive ART treatment with a different degree of CD4+ T cell reconstitution. Total auto‐IgG binding on CD4+ T cell surfaces and its associated apoptosis and CD4+ T cell recovery were analyzed by flow cytometry ex vivo. Total IgGs from plasma were tested for their binding capacities to CD4+ T cell surfaces and their mediation to CD4+ T cell death through NK cell cytotoxicity in vitro. HIV+ subjects had increased surface binding of auto‐IgGs on CD4+ T cells compared with healthy controls, and IgG binding was associated with elevated CD4+ T cell apoptosis in HIV+ subjects but not in healthy controls. Plasma IgGs from HIV+ subjects bound to CD4+ T cells and induced cell apoptosis through NK cytotoxicity in vitro. Soluble CD4 (sCD4) preincubation prevented NK cell‐mediated CD4+ T cell death. Our results suggest that plasma autoantibodies may play a role in some HIV+ patients with poor CD4+ T cell recovery under viral‐suppressive ART.