{"doi":"10.1126/science.adk3248","title":"Regulatory T cells constrain T cells of shared specificity to enforce tolerance during infection","abstract":"During infections, CD4 + Foxp3 + regulatory T (T reg ) cells must control autoreactive CD4 + conventional T (T conv ) cell responses against self-peptide antigens while permitting those against pathogen-derived “nonself” peptides. We defined the basis of this selectivity using mice in which T reg cells reactive to a single prostate-specific self-peptide were selectively depleted. We found that self-peptide–specific T reg cells were dispensable for the control of T conv cells of matched specificity at homeostasis. However, they were required to control such T conv cells and prevent autoimmunity toward the prostate after exposure to elevated self-peptide during infection. Notably, the T reg cell response to self-peptide did not affect protective T conv cell responses to a pathogen-derived peptide. Thus, self-peptide–specific T reg cells promoted self-nonself discrimination during infection by selectively controlling T conv cells of shared self-specificity.","journal":"Science","year":2025,"id":509757,"datarank":0.8209967820964668,"base_score":3.332204510175204,"endowment":3.332204510175204,"self_citation_contribution":0.49983067652628066,"citation_network_contribution":0.32116610557018616,"self_endowment_contribution":0.49983067652628066,"citer_contribution":0.32116610557018616,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"citer_count":27,"citers_with_citation_signal":12,"citers_with_endowment":12,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9516,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE235974"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1248912,"name":"Nicole Pagane","orcid":"0009-0007-0079-0515","position":1,"is_corresponding":false},{"id":339433,"name":"Matthew T. Walker","orcid":"0000-0002-0921-5812","position":2,"is_corresponding":false},{"id":1364816,"name":"Nicole K. Ganci","orcid":"0000-0002-8037-607X","position":3,"is_corresponding":false},{"id":289000,"name":"Christine H. Miller","orcid":"0000-0003-2176-9516","position":4,"is_corresponding":false},{"id":273969,"name":"Eric Gai","orcid":"0000-0002-9011-0347","position":5,"is_corresponding":false},{"id":1364817,"name":"Donald M. Rodriguez","orcid":"0000-0002-2534-1480","position":6,"is_corresponding":false},{"id":1365668,"name":"Bridgett K. Ryan-Payseur","orcid":null,"position":7,"is_corresponding":false},{"id":774951,"name":"Ryan K. Duncombe","orcid":"0000-0001-7414-0987","position":8,"is_corresponding":false},{"id":563084,"name":"Erin J. Adams","orcid":"0000-0002-6271-8574","position":9,"is_corresponding":false},{"id":552662,"name":"Mark Maienschein‐Cline","orcid":"0000-0001-6619-6788","position":10,"is_corresponding":false},{"id":475450,"name":"Nancy E. Freitag","orcid":"0000-0003-1322-3978","position":11,"is_corresponding":false},{"id":228444,"name":"Ronald N. Germain","orcid":"0000-0003-1495-9143","position":12,"is_corresponding":false},{"id":236794,"name":"Harikesh S. Wong","orcid":"0000-0003-0313-6600","position":13,"is_corresponding":false},{"id":289004,"name":"Peter A. Savage","orcid":"0000-0002-2506-7717","position":14,"is_corresponding":false},{"id":289001,"name":"David E. J. Klawon","orcid":"0000-0001-7953-2525","position":0,"is_corresponding":true}],"reference_count":83,"raw_metadata":null,"created_at":"2026-07-19T02:47:30.942539Z","pmid":"40014689","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":[]}