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

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Abstract

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-naïve HIV-infected patients with different CD4+T cell counts, 97 nucleoside-reverse 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.

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