{"doi":"10.1084/jem.20211574","title":"TGF-β regulates the stem-like state of PD-1+ TCF-1+ virus-specific CD8 T cells during chronic infection","abstract":"Recent studies have defined a novel population of PD-1+ TCF-1+ stem-like CD8 T cells in chronic infections and cancer. These quiescent cells reside in lymphoid tissues, are critical for maintaining the CD8 T cell response under conditions of persistent antigen, and provide the proliferative burst after PD-1 blockade. Here we examined the role of TGF-β in regulating the differentiation of virus-specific CD8 T cells during chronic LCMV infection of mice. We found that TGF-β signaling was not essential for the generation of the stem-like CD8 T cells but was critical for maintaining the stem-like state and quiescence of these cells. TGF-β regulated the unique transcriptional program of the stem-like subset, including upregulation of inhibitory receptors specifically expressed on these cells. TGF-β also promoted the terminal differentiation of exhausted CD8 T cells by suppressing the effector-associated program. Together, the absence of TGF-β signaling resulted in significantly increased accumulation of effector-like CD8 T cells. These findings have implications for immunotherapies in general and especially for T cell therapy against chronic infections and cancer.","journal":"The Journal of Experimental Medicine","year":2022,"id":235193,"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":84,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9499,"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":226154,"name":"William Henry Hudson","orcid":"0000-0002-2513-1213","position":1,"is_corresponding":false},{"id":240995,"name":"Haydn Kissick","orcid":"0000-0001-7624-5598","position":2,"is_corresponding":false},{"id":516709,"name":"Christopher B. Medina","orcid":"0000-0001-7441-9232","position":3,"is_corresponding":false},{"id":80085,"name":"Antonio P. Baptista","orcid":"0000-0001-8182-8982","position":4,"is_corresponding":false},{"id":315978,"name":"Chaoyu Ma","orcid":null,"position":5,"is_corresponding":false},{"id":314396,"name":"Wei Liao","orcid":"0000-0002-8828-011X","position":6,"is_corresponding":false},{"id":228444,"name":"Ronald N. Germain","orcid":"0000-0003-1495-9143","position":7,"is_corresponding":false},{"id":18142,"name":"Shannon J. Turley","orcid":"0000-0002-0307-908X","position":8,"is_corresponding":false},{"id":256588,"name":"Nu Zhang","orcid":"0000-0001-9695-210X","position":9,"is_corresponding":false},{"id":226172,"name":"Rafi Ahmed","orcid":"0000-0002-9591-2621","position":10,"is_corresponding":false},{"id":852799,"name":"Yinghong Hu","orcid":"0000-0001-9714-8957","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-19T00:21:48.116752Z","pmid":"35980386","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":[]}