{"doi":"10.1101/2020.03.05.979146","title":"Functional delineation of tissue-resident CD8 <sup>+</sup> T cell heterogeneity during infection and cancer","abstract":"Abstract Unremitting defense against diverse pathogens and malignancies requires a dynamic and durable immune response. Tissue-resident memory CD8 + T cells (T rm ) afford robust protection against infection and cancer progression through continuous surveillance of non-lymphoid tissues. Here, we provide insight into how T rm confer potent and persistent immunity through partitioning of distinct cellular subsets differing in longevity, effector function, and multipotency. Antigen-specific CD8 + T cells localized to the epithelium of the small intestine are primarily comprised of a shorter-lived effector population most prominent early following both acute viral and bacterial infections, and a longer-lived Id3 hi T rm population that subsequently accumulates at later memory timepoints. We define regulatory gene-programs driving these distinct T rm states, and further clarify roles for Blimp1, T-bet, Id2, and Id3 in supporting and maintaining intestinal T rm heterogeneity during infection. Further, through single-cell RNAseq analysis we demonstrate that tumor-infiltrating lymphocytes broadly differentiate into discrete populations of short-lived and long-lived T rm -like subsets, which share qualities with terminally-exhausted and progenitor-exhausted cells, respectively. As the clinical relevance of T rm continues to widen from acute infections to settings of chronic inflammation and malignancy, clarification of the spectrum of phenotypic and functional states exhibited by CD8 + T cells that reside in non-lymphoid tissues will provide a framework for understanding their regulation and identity in diverse pathophysiological contexts.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":124681,"datarank":0.20156559297518317,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.03677374967496672,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.03677374967496672,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":1,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9492,"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":270803,"name":"Clara Toma","orcid":"0000-0002-9957-4826","position":1,"is_corresponding":false},{"id":236064,"name":"Zhaoren He","orcid":"0000-0001-5521-1460","position":2,"is_corresponding":false},{"id":238814,"name":"Nadia S. Kurd","orcid":null,"position":3,"is_corresponding":false},{"id":569834,"name":"Quynh Nguyen","orcid":"0000-0002-5975-3600","position":4,"is_corresponding":false},{"id":569835,"name":"Bryan McDonald","orcid":"0000-0003-1744-3433","position":5,"is_corresponding":false},{"id":236075,"name":"Lauren K. Quezada","orcid":"0000-0003-2056-6055","position":6,"is_corresponding":false},{"id":242483,"name":"Christella E. Widjaja","orcid":"0000-0002-0655-2557","position":7,"is_corresponding":false},{"id":441549,"name":"Deborah A. Witherden","orcid":"0000-0003-2545-1935","position":8,"is_corresponding":false},{"id":570468,"name":"John T. Crowl","orcid":null,"position":9,"is_corresponding":false},{"id":43290,"name":"G Yeo","orcid":null,"position":10,"is_corresponding":false},{"id":225253,"name":"John T. Chang","orcid":"0000-0003-0873-6218","position":11,"is_corresponding":false},{"id":236067,"name":"Kyla Omilusik","orcid":"0000-0003-3675-048X","position":12,"is_corresponding":false},{"id":61594,"name":"Ananda W. Goldrath","orcid":"0000-0002-5900-508X","position":13,"is_corresponding":false},{"id":84671,"name":"J. Justin Milner","orcid":"0000-0002-0752-2130","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:15:11.632153Z","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":[]}