Distinct Mitochondrial Disturbance in CD4+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 CD4T and CD8T 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 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.


RESULTS
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.


CONCLUSIONS
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.
*Clinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China; †College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China; ‡Clinical Center for HIV/AIDS, Capital Medical University, Beijing, China; §Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China; and ‖Department of Infectious Diseases, Peking University Ditan Teaching, Hospital, Beijing, China.
Fengting
F
Yu
Yu
Y
Hao
Hongxin
H
Zhao
Jiang
J
Xiao
Ning
N
Han
Yu
Y
Zhang
Guorui
G
Dai
Xuejing
X
Chong
Hui
H
Zeng
Fujie
F
Zhang
D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D001699:Biometry; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial; D008875:Middle Aged; D008928:Mitochondria / Q000502:physiology* / Q000648:ultrastructure*; D017382:Reactive Oxygen Species / Q000032:analysis; D014838:Volunteers; D055815:Young Adult
D044966:Anti-Retroviral Agents; D017382:Reactive Oxygen Species