Compromised Glycolysis in Memory CD4+ T cells Derived from HIV-infected Immunological Non-Responders to Highly Active Antiretroviral Therapy.

Abstract

HAART-treated HIV-infected individuals, known as «immunological non-responders» (INR), fail to restore CD4+ T cell counts despite effective viral control. Incomplete immune restoration in INR is usually linked to low-productive proliferation of memory CD4+ T lymphocytes. Given that CD4+ T cell ability to divide critically depends on the glycolytic pathway, we aimed to determine the levels of glucose uptake and glycolysis in memory CD4+ T cells of INR. Two groups of HIV-infected HAART-treated subjects were studied: INR and immunological responders, with a healthy controls group comprising uninfected volunteers. The results showed that INR had the highest activation level in memory CD4+ T cells and the greatest glucose uptake. Short-term phytohemagglutinin stimulation provoked an increase in aerobic glycolysis in memory CD4+ T lymphocytes. Nevertheless, we found significantly reduced aerobic glycolysis in activated memory CD4+ Т cells of INR. Hence in INR, there is a discrepancy between the highly activated phenotype of memory CD4+ T lymphocytes and their glycolytic activity.