{"doi":"10.1101/2020.01.07.894535","title":"TCF-1 regulates the stem-like memory potential of HIV-specific CD8+ T cells in elite controllers","abstract":"Abstract Although many HIV cure strategies seek to expand HIV-specific CD8+ T cells to control the virus, all are likely to fail if cellular exhaustion is not prevented. A loss in stem-like memory properties (i.e., the ability to proliferate and generate secondary effector cells) is a key feature of exhaustion; little is known, however, about how these properties are regulated in human virus-specific CD8+ T cells. We found that virus-specific CD8+ T cells from humans and non-human primates naturally controlling HIV/SIV infection express more of the transcription factor, TCF-1, than non-controllers. HIV-specific CD8+ T cell TCF-1 expression correlated with memory marker expression and proliferative capacity and declined with antigenic stimulation. CRISPR-Cas9 editing of TCF-1 in human primary T cells demonstrated a direct role in regulating expansion capacity. Collectively, these data suggest that TCF-1 controls the stem-like memory properties of HIV-specific CD8+ T cells and provides a rationale for enhancing this pathway in T cell-based therapeutic strategies for HIV. One Sentence Summary TCF-1 is highly expressed in HIV-specific CD8+ T cells from elite controllers and directly regulates human CD8+ T cell expansion capacity in response to T cell receptor stimulation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":123376,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9438,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":290818,"name":"Christian Deo T. 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Koup","orcid":"0000-0002-3090-7282","position":17,"is_corresponding":false},{"id":277153,"name":"Daniel C. Douek","orcid":"0000-0001-5575-8634","position":18,"is_corresponding":false},{"id":241757,"name":"Jason M. Brenchley","orcid":"0000-0001-8357-2984","position":19,"is_corresponding":false},{"id":244983,"name":"Rafick‐Pierre Sékaly","orcid":"0000-0002-7816-4828","position":20,"is_corresponding":false},{"id":24132,"name":"Satish K. Pillai","orcid":"0000-0001-8770-7014","position":21,"is_corresponding":false},{"id":30775,"name":"Alexander Marson","orcid":"0000-0002-2734-5776","position":22,"is_corresponding":false},{"id":71691,"name":"Steven G. Deeks","orcid":"0000-0001-6371-747X","position":23,"is_corresponding":false},{"id":39798,"name":"Joseph M. McCune","orcid":"0000-0002-9388-070X","position":24,"is_corresponding":false},{"id":239685,"name":"Peter W. Hunt","orcid":"0000-0002-4571-4870","position":25,"is_corresponding":false},{"id":271007,"name":"Rachel L. Rutishauser","orcid":"0000-0003-3596-059X","position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":null,"created_at":"2026-07-18T23:14:59.547352Z","pmid":null,"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":[]}