{"doi":"10.7554/elife.65615","title":"CD8+ T cell self-tolerance permits responsiveness but limits tissue damage","abstract":"Self-specific CD8 + T cells can escape clonal deletion, but the properties and capabilities of such cells in a physiological setting are unclear. We characterized polyclonal CD8 + T cells specific for the melanocyte antigen tyrosinase-related protein 2 (Trp2) in mice expressing or lacking this enzyme (due to deficiency in Dct , which encodes Trp2). Phenotypic and gene expression profiles of pre-immune Trp2/K b -specific cells were similar; the size of this population was only slightly reduced in wild-type (WT) compared to Dct -deficient ( Dct -/- ) mice. Despite comparable initial responses to Trp2 immunization, WT Trp2/K b -specific cells showed blunted expansion and less readily differentiated into a CD25 + proliferative population. Functional self-tolerance clearly emerged when assessing immunopathology: adoptively transferred WT Trp2/K b -specific cells mediated vitiligo much less efficiently. Hence, CD8 + T cell self-specificity is poorly predicted by precursor frequency, phenotype, or even initial responsiveness, while deficient activation-induced CD25 expression and other gene expression characteristics may help to identify functionally tolerant cells.","journal":"eLife","year":2021,"id":182670,"datarank":0.6587761199973066,"base_score":2.70805020110221,"endowment":2.70805020110221,"self_citation_contribution":0.40620753016533157,"citation_network_contribution":0.252568589831975,"self_endowment_contribution":0.40620753016533157,"citer_contribution":0.252568589831975,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":14,"citers_with_citation_signal":11,"citers_with_endowment":11,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9586,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE171221"]},"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":427690,"name":"Kristina S. Burrack","orcid":"0000-0002-6931-226X","position":1,"is_corresponding":false},{"id":462102,"name":"Todd P. Knutson","orcid":"0000-0001-8431-9964","position":2,"is_corresponding":false},{"id":586845,"name":"Henrique Borges da Silva","orcid":"0000-0001-9424-3326","position":3,"is_corresponding":false},{"id":586846,"name":"Katharine E. Block","orcid":"0000-0001-9488-3577","position":4,"is_corresponding":false},{"id":515227,"name":"Stephen D. O’Flanagan","orcid":"0000-0002-9286-1208","position":5,"is_corresponding":false},{"id":587418,"name":"Katie R Stagliano","orcid":null,"position":6,"is_corresponding":false},{"id":587419,"name":"Arthur A. Hurwitz","orcid":null,"position":7,"is_corresponding":false},{"id":586847,"name":"Ross B. Fulton","orcid":"0000-0002-0705-2917","position":8,"is_corresponding":false},{"id":577564,"name":"Kristin R. Renkema","orcid":"0000-0003-4000-3356","position":9,"is_corresponding":false},{"id":235915,"name":"Stephen C. Jameson","orcid":"0000-0001-9137-1146","position":10,"is_corresponding":false},{"id":586844,"name":"Emily N Truckenbrod","orcid":"0000-0002-3819-6307","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-18T23:48:13.605421Z","pmid":"33929324","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":[]}