Metabolic Features of Activated Memory CD4+ T-Cells Derived from HIV-Infected Immunological Non-responders to Highly Active Antiretroviral Therapy

Abstract

Immunological non-responders (INR) are HIV-infected subjects that fail to restore CD4+ T-cell counts despite undetectable HIV viral load, which is controlled by highly active antiretroviral therapy (HAART). In INR, impaired immune restoration is linked to low-productive proliferation of memory CD4+ T-lymphocytes. Taking into account that T-cell ability to divide depends on the activity of metabolic pathways, we aimed to determine rates of mitochondrial respiration and glycolysis in memory CD4+ T-cells of INR. Two groups of HIV-infected HAART-treated patients were studied: immunological non-responders and subjects with an adequate immunological response to therapy (immunological responders - IR). Control (C) group comprised uninfected volunteers. In both groups of HIV-infected patients glycolytic activity of memory CD4+ T-cells was lower than that in C. Mitochondrial respiration rate in memory CD4+ T-cells derived from IR was comparable to that of C at basal state, however, after stimulation IR failed to reach the values of uninfected subjects. INR had the lowest mitochondrial respiration rate both at basal state and after stimulation. Taken together, the data presented herein demonstrate that low regenerative potential of memory CD4+ T-cells derived from INR might be linked to diminished lymphocytes' metabolic activity.