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.
| Identifer | oai:union.ndltd.org:ETSU/oai:dc.etsu.edu:etsu-works-10844 |
| Date | 04 May 2021 |
| Creators | Zhao, Juan, Schank, Madison, Wang, Ling, Li, Zhengke, Nguyen, Lam N., Dang, Xindi, Cao, Dechao, Khanal, Sushant, Nguyen, Lam N., Thakuri, Bal K., Ogbu, Stella C., Lu, Zeyuan, Wu, Xiao Y., Morrison, Zheng D., El Gazzar, Mohamed, Liu, Ying, Zhang, Jinyu, Ning, Shunbin |
| Publisher | Digital Commons @ East Tennessee State University |
| Source Sets | East Tennessee State University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | ETSU Faculty Works |
| Rights | http://creativecommons.org/licenses/by/4.0/ |
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