{"doi":"10.3389/fimmu.2021.658420","title":"Mitochondrial Functions Are Compromised in CD4 T Cells From ART-Controlled PLHIV","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.","journal":"Frontiers in Immunology","year":2021,"id":159013,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":43,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9527,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":336311,"name":"Madison Schank","orcid":"0000-0001-9017-3180","position":1,"is_corresponding":false},{"id":336313,"name":"Ling Wang","orcid":"0000-0001-7861-2769","position":2,"is_corresponding":false},{"id":336314,"name":"Zhengke Li","orcid":"0000-0001-5560-343X","position":3,"is_corresponding":false},{"id":336316,"name":"Lam Nhat Nguyen","orcid":"0000-0002-8419-8354","position":4,"is_corresponding":false},{"id":338131,"name":"Xindi Dang","orcid":null,"position":5,"is_corresponding":false},{"id":336315,"name":"Dechao Cao","orcid":"0000-0001-5038-1807","position":6,"is_corresponding":false},{"id":336317,"name":"Sushant Khanal","orcid":"0000-0001-8028-6034","position":7,"is_corresponding":false},{"id":338132,"name":"Lam Ngoc Thao Nguyen","orcid":null,"position":8,"is_corresponding":false},{"id":336318,"name":"Bal Krishna Chand Thakuri","orcid":"0000-0003-3768-279X","position":9,"is_corresponding":false},{"id":336319,"name":"Stella C. Ogbu","orcid":"0000-0001-8798-5305","position":10,"is_corresponding":false},{"id":336320,"name":"Zeyuan Lu","orcid":"0000-0003-4572-6289","position":11,"is_corresponding":false},{"id":338133,"name":"Xiao Y. Wu","orcid":null,"position":12,"is_corresponding":false},{"id":338134,"name":"Zheng D. Morrison","orcid":null,"position":13,"is_corresponding":false},{"id":338135,"name":"Mohamed El Gazzar","orcid":null,"position":14,"is_corresponding":false},{"id":669133,"name":"Ying Liu","orcid":"0000-0002-9391-9707","position":15,"is_corresponding":false},{"id":350576,"name":"Jinyu Zhang","orcid":"0009-0005-8571-9368","position":16,"is_corresponding":false},{"id":336322,"name":"Shunbin Ning","orcid":"0000-0001-5484-5779","position":17,"is_corresponding":false},{"id":336323,"name":"Jonathan P. Moorman","orcid":"0000-0002-6102-6541","position":18,"is_corresponding":false},{"id":336324,"name":"Zhi Q. Yao","orcid":"0000-0002-1848-1071","position":19,"is_corresponding":false},{"id":336312,"name":"Juan Zhao","orcid":"0000-0002-1809-3124","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-18T23:44:35.165422Z","pmid":"34017335","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}