{"doi":"10.1002/eji.202048630","title":"Broadly reactive human CD4 <sup>+</sup> T cells against Enterobacteriaceae are found in the naïve repertoire and are clonally expanded in the memory repertoire","abstract":"Abstract Enterobacteriaceae are a large family of Gram‐negative bacteria that includes both commensals and opportunistic pathogens. The latter can cause severe nosocomial infections, with outbreaks of multi‐antibiotics resistant strains, thus being a major public health threat. In this study, we report that Enterobacteriaceae‐reactive memory Th cells were highly enriched in a CCR6 + CXCR3 + Th1*/17 cell subset and produced IFN‐γ, IL‐17A, and IL‐22. This T cell subset was severely reduced in septic patients with K. pneumoniae bloodstream infection who also selectively lacked circulating K. pneumonie ‐reactive T cells. By combining heterologous antigenic stimulation, single cell cloning and TCR Vβ sequencing, we demonstrate that a large fraction of memory Th cell clones was broadly cross‐reactive to several Enterobacteriaceae species. These cross‐reactive Th cell clones were expanded in vivo and a large fraction of them recognized the conserved outer membrane protein A antigen. Interestingly, Enterobacteriaceae broadly cross‐reactive T cells were also prominent among in vitro primed naïve T cells. Collectively, these data point to the existence of immunodominant T cell epitopes shared among different Enterobacteriaceae species and targeted by cross‐reactive T cells that are readily found in the pre‐immune repertoire and are clonally expanded in the memory repertoire.","journal":"European Journal of Immunology","year":2020,"id":103619,"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":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9583,"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":505560,"name":"Jérémie D. Goldstein","orcid":null,"position":1,"is_corresponding":false},{"id":505561,"name":"Greta Durini","orcid":null,"position":2,"is_corresponding":false},{"id":504578,"name":"David Jarrossay","orcid":"0000-0002-0924-6395","position":3,"is_corresponding":false},{"id":505562,"name":"Franca Baggi Menozzi","orcid":null,"position":4,"is_corresponding":false},{"id":504579,"name":"Mario Venditti","orcid":"0000-0003-2639-0281","position":5,"is_corresponding":false},{"id":504580,"name":"Alessandro Russo","orcid":"0000-0003-3846-4620","position":6,"is_corresponding":false},{"id":475137,"name":"Marco Falcone","orcid":"0000-0003-3813-8796","position":7,"is_corresponding":false},{"id":217935,"name":"Antonio Lanzavecchia","orcid":"0000-0002-3041-7240","position":8,"is_corresponding":false},{"id":504581,"name":"Maria Cristina Gagliardi","orcid":"0000-0003-3176-5439","position":9,"is_corresponding":false},{"id":504582,"name":"Daniela Latorre","orcid":"0000-0003-1031-1534","position":10,"is_corresponding":false},{"id":73799,"name":"Federica Sallusto","orcid":"0000-0003-3750-2752","position":11,"is_corresponding":false},{"id":504577,"name":"Antonino Cassotta","orcid":"0000-0001-8674-4294","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-18T22:42:48.999009Z","pmid":"33226131","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":[]}