Mitochondrial Functions Are Compromised in CD4 T Cells From ART-Controlled PLHIV
Copyright © 2021 Zhao, Schank, Wang, Li, Nguyen, Dang, Cao, Khanal, Nguyen, Thakuri, Ogbu, Lu, Wu, Morrison, Gazzar, Liu, Zhang, Ning, Moorman and Yao..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Frontiers in immunology - 12(2021) vom: 31., Seite 658420 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhao, Juan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 30.09.2021 Date Revised 30.09.2021 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.3389/fimmu.2021.658420 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2021 Zhao, Schank, Wang, Li, Nguyen, Dang, Cao, Khanal, Nguyen, Thakuri, Ogbu, Lu, Wu, Morrison, Gazzar, Liu, Zhang, Ning, Moorman and Yao. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a HIV | |
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| 700 | 1 | |a Nguyen, Lam Nhat |e verfasserin |4 aut | |
| 700 | 1 | |a Dang, Xindi |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Dechao |e verfasserin |4 aut | |
| 700 | 1 | |a Khanal, Sushant |e verfasserin |4 aut | |
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| 700 | 1 | |a Wu, Xiao Y |e verfasserin |4 aut | |
| 700 | 1 | |a Morrison, Zheng D |e verfasserin |4 aut | |
| 700 | 1 | |a Gazzar, Mohamed El |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jinyu |e verfasserin |4 aut | |
| 700 | 1 | |a Ning, Shunbin |e verfasserin |4 aut | |
| 700 | 1 | |a Moorman, Jonathan P |e verfasserin |4 aut | |
| 700 | 1 | |a Yao, Zhi Q |e verfasserin |4 aut | |
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