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

Background: 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 CD4(+)T and CD8(+) T cells caused by different levels of HIV progression and ART is poorly understood. Methods: Blood samples were obtained from 97 ART-naive HIV-infected patients with different CD4(+)T cell counts, 97 nucleosidereverse transcriptase inhibitors-exposed HIV-infected patients, and 25 HIV-negative subjects. MMP, ROS, and MM in CD4(+)T and CD8+ T cells were assessed by flow cytometry. Results: In healthy subjects, the levels of MMP and MM in CD4(+)T cells were higher than those in CD8(+)T cells. HIV infection led to an increase in MM in CD4(+)T and CD8(+)T cells, but mainly influenced MMP in CD8(+) T cells and ROS accumulation in CD4(+)T cells. MM in CD4(+)T and CD8(+) T cells gradually increased after the loss of CD4(+)T cells. Although the dynamic changes in MMP in CD4+ T cells were different from those in CD8(+) T cells during highly active ART, MM in both CD4(+)T and CD8(+) T cells was significantly decreased after 2 years of therapy, but increased again after 3 years. Conclusions: HIV infection and antiretroviral therapy both led to mitochondrial disturbances in CD4(+)T cells and CD8(+) T cells; however, the abnormal changes in mitochondrial parameters in CD4(+)T cells were different from those in CD8(+) T cells caused by HIV infection and antiretroviral therapy.12th Five Year Plan-Exploration and Application of Optimized Pediatric Antiretroviral Treatment [2012ZX10001004]; National Natural Science Foundation of China [81371804]; The National Clinical Key Department of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaSCI(E)ARTICLE2206-2127