{"doi":"10.1172/jci157549","title":"Reprogramming dysfunctional CD8+ T cells to promote properties associated with natural HIV control","abstract":"Virus-specific CD8+ T cells play a central role in HIV-1 natural controllers to maintain suppressed viremia in the absence of antiretroviral therapy. These cells display a memory program that confers them stemness properties, high survival, polyfunctionality, proliferative capacity, metabolic plasticity, and antiviral potential. The development and maintenance of such qualities by memory CD8+ T cells appear crucial to achieving natural HIV-1 control. Here, we show that targeting the signaling pathways Wnt/transcription factor T cell factor 1 (Wnt/TCF-1) and mTORC through GSK3 inhibition to reprogram HIV-specific CD8+ T cells from noncontrollers promoted functional capacities associated with natural control of infection. Features of such reprogrammed cells included enrichment in TCF-1+ less-differentiated subsets, a superior response to antigen, enhanced survival, polyfunctionality, metabolic plasticity, less mTORC1 dependency, an improved response to γ-chain cytokines, and a stronger HIV-suppressive capacity. Thus, such CD8+ T cell reprogramming, combined with other available immunomodulators, might represent a promising strategy for adoptive cell therapy in the search for an HIV-1 cure.","journal":"Journal of Clinical Investigation","year":2022,"id":241738,"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":40,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9421,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":369705,"name":"Caroline Passaes","orcid":"0000-0002-0813-2521","position":1,"is_corresponding":false},{"id":871228,"name":"Valérie Monceaux","orcid":"0000-0002-8599-2146","position":2,"is_corresponding":false},{"id":505729,"name":"Stevenn Volant","orcid":null,"position":3,"is_corresponding":false},{"id":863045,"name":"Faroudy Boufassa","orcid":"0000-0002-3650-6105","position":4,"is_corresponding":false},{"id":863047,"name":"Pierre de Truchis","orcid":"0000-0002-0038-2905","position":5,"is_corresponding":false},{"id":871940,"name":"Morgane Marcou","orcid":null,"position":6,"is_corresponding":false},{"id":871941,"name":"Katia Bourdic","orcid":null,"position":7,"is_corresponding":false},{"id":651126,"name":"Laurence Weiss","orcid":"0000-0003-3213-2692","position":8,"is_corresponding":false},{"id":871942,"name":"Corinne Jung","orcid":null,"position":9,"is_corresponding":false},{"id":871229,"name":"Christine Bourgeois","orcid":"0000-0003-1146-6087","position":10,"is_corresponding":false},{"id":200787,"name":"Cécile Goujard","orcid":null,"position":11,"is_corresponding":false},{"id":40989,"name":"Laurence Meyer","orcid":"0000-0001-5707-2062","position":12,"is_corresponding":false},{"id":410086,"name":"Michaela Müller‐Trutwin","orcid":"0000-0002-3854-2396","position":13,"is_corresponding":false},{"id":617938,"name":"Olivier Lambotte","orcid":"0000-0003-4425-8516","position":14,"is_corresponding":false},{"id":871943,"name":"Asier Sáez-Cirión","orcid":null,"position":15,"is_corresponding":false},{"id":871227,"name":"Federico Perdomo-Celis","orcid":"0000-0003-0119-8306","position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":null,"created_at":"2026-07-19T00:23:00.865267Z","pmid":"35380989","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":[]}