Frontiers in Immunology (May 2021)
Mitochondrial Functions Are Compromised in CD4 T Cells From ART-Controlled PLHIV
- Juan Zhao,
- Juan Zhao,
- Madison Schank,
- Madison Schank,
- Ling Wang,
- Ling Wang,
- Zhengke Li,
- Zhengke Li,
- Lam Nhat Nguyen,
- Lam Nhat Nguyen,
- Xindi Dang,
- Xindi Dang,
- Dechao Cao,
- Dechao Cao,
- Sushant Khanal,
- Sushant Khanal,
- Lam Ngoc Thao Nguyen,
- Lam Ngoc Thao Nguyen,
- Bal Krishna Chand Thakuri,
- Bal Krishna Chand Thakuri,
- Stella C. Ogbu,
- Stella C. Ogbu,
- Zeyuan Lu,
- Zeyuan Lu,
- Xiao Y. Wu,
- Xiao Y. Wu,
- Zheng D. Morrison,
- Zheng D. Morrison,
- Mohamed El Gazzar,
- Mohamed El Gazzar,
- Ying Liu,
- Ying Liu,
- Jinyu Zhang,
- Jinyu Zhang,
- Shunbin Ning,
- Shunbin Ning,
- Jonathan P. Moorman,
- Jonathan P. Moorman,
- Jonathan P. Moorman,
- Zhi Q. Yao,
- Zhi Q. Yao,
- Zhi Q. Yao
Affiliations
- Juan Zhao
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Juan Zhao
- Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Madison Schank
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Madison Schank
- Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Ling Wang
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Ling Wang
- Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Zhengke Li
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Zhengke Li
- Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Lam Nhat Nguyen
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Lam Nhat Nguyen
- Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Xindi Dang
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Xindi Dang
- Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Dechao Cao
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Dechao Cao
- Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Sushant Khanal
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Sushant Khanal
- Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Lam Ngoc Thao Nguyen
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Lam Ngoc Thao Nguyen
- Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Bal Krishna Chand Thakuri
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Bal Krishna Chand Thakuri
- Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Stella C. Ogbu
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Stella C. Ogbu
- Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Zeyuan Lu
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Zeyuan Lu
- Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Xiao Y. Wu
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Xiao Y. Wu
- Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Zheng D. Morrison
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Zheng D. Morrison
- Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Mohamed El Gazzar
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Mohamed El Gazzar
- Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Ying Liu
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Ying Liu
- Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Johnson City, TN, United States
- Jinyu Zhang
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Jinyu Zhang
- Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Shunbin Ning
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Shunbin Ning
- Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Jonathan P. Moorman
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Jonathan P. Moorman
- Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Jonathan P. Moorman
- Hepatitis (HCV/HBV/HIV) Program, James H. Quillen VA Medical Center, Department of Veterans Affairs, Johnson City, TN, United States
- Zhi Q. Yao
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Zhi Q. Yao
- Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
- Zhi Q. Yao
- Hepatitis (HCV/HBV/HIV) Program, James H. Quillen VA Medical Center, Department of Veterans Affairs, Johnson City, TN, United States
- DOI
- https://doi.org/10.3389/fimmu.2021.658420
- Journal volume & issue
-
Vol. 12
Abstract
The hallmark of HIV/AIDS is a gradual depletion of CD4 T cells. Despite effective control by antiretroviral therapy (ART), a significant subgroup of people living with HIV (PLHIV) fails to achieve complete immune reconstitution, deemed as immune non-responders (INRs). The mechanisms underlying incomplete CD4 T cell recovery in PLHIV remain unclear. In this study, CD4 T cells from PLHIV were phenotyped and functionally characterized, focusing on their mitochondrial functions. The results show that while total CD4 T cells are diminished, cycling cells are expanded in PLHIV, especially in INRs. HIV-INR CD4 T cells are more activated, displaying exhausted and senescent phenotypes with compromised mitochondrial functions. Transcriptional profiling and flow cytometry analysis showed remarkable repression of mitochondrial transcription factor A (mtTFA) in CD4 T cells from PLHIV, leading to abnormal mitochondrial and T cell homeostasis. These results demonstrate a sequential cellular paradigm of T cell over-activation, proliferation, exhaustion, senescence, apoptosis, and depletion, which correlates with compromised mitochondrial functions. Therefore, reconstituting the mtTFA pathway may provide an adjunctive immunological approach to revitalizing CD4 T cells in ART-treated PLHIV, especially in INRs.
Keywords
