Distinct Mitochondrial Disturbance in CD4+T and CD8+T Cells From HIV-Infected Patients

Abstract

Mitochondrial dysfunction has frequently been found in HIV-infected patients regardless of whether they received antiretroviral therapy (ART). Accumulating evidence suggests that HIV-infected patients exhibit marked changes in mitochondrial membrane potential (MMP), reactive oxygen species (ROS) accumulation, adenosine triphosphate generation, mitochondrial mass (MM), mitochondrial DNA, etc. However, mitochondrial toxicity in CD4T and CD8T cells caused by different levels of HIV progression and ART is poorly understood. Blood samples were obtained from 97 ART-naïve HIV-infected patients with different CD4T cell counts, 97 nucleoside-reverse transcriptase inhibitors-exposed HIV-infected patients, and 25 HIV-negative subjects. MMP, ROS, and MM in CD4T and CD8T cells were assessed by flow cytometry. In healthy subjects, the levels of MMP and MM in CD4T cells were higher than those in CD8T cells. HIV infection led to an increase in MM in CD4T and CD8T cells, but mainly influenced MMP in CD8T cells and ROS accumulation in CD4T cells. MM in CD4T and CD8T cells gradually increased after the loss of CD4T cells. Although the dynamic changes in MMP in CD4T cells were different from those in CD8T cells during highly active ART, MM in both CD4T and CD8T cells was significantly decreased after 2 years of therapy, but increased again after 3 years. HIV infection and antiretroviral therapy both led to mitochondrial disturbances in CD4T cells and CD8T cells; however, the abnormal changes in mitochondrial parameters in CD4+T cells were different from those in CD8T cells caused by HIV infection and antiretroviral therapy.