{"doi":"10.1016/j.ebiom.2021.103746","title":"CD4+CCR6+ T cells dominate the BCG-induced transcriptional signature","abstract":"BACKGROUND: The century-old Mycobacterium bovis Bacillus Calmette-Guerin (BCG) remains the only licensed vaccine against tuberculosis (TB). Despite this, there is still a lot to learn about the immune response induced by BCG, both in terms of phenotype and specificity. METHODS: We investigated immune responses in adult individuals pre and 8 months post BCG vaccination. We specifically determined changes in gene expression, cell subset composition, DNA methylome, and the TCR repertoire induced in PBMCs and CD4 memory T cells associated with antigen stimulation by either BCG or a Mycobacterium tuberculosis (Mtb)-derived peptide pool. FINDINGS: Following BCG vaccination, we observed increased frequencies of CCR6+ CD4 T cells, which includes both Th1* (CXCR3+CCR6+) and Th17 subsets, and mucosal associated invariant T cells (MAITs). A large number of immune response genes and pathways were upregulated post BCG vaccination with similar patterns observed in both PBMCs and memory CD4 T cells, thus suggesting a substantial role for CD4 T cells in the cellular response to BCG. These upregulated genes and associated pathways were also reflected in the DNA methylome. We described both qualitative and quantitative changes in the BCG-specific TCR repertoire post vaccination, and importantly found evidence for similar TCR repertoires across different subjects. INTERPRETATION: The immune signatures defined herein can be used to track and further characterize immune responses induced by BCG, and can serve as reference for benchmarking novel vaccination strategies.","journal":"EBioMedicine","year":2021,"id":176972,"datarank":0.4636563680037475,"base_score":3.091042453358316,"endowment":3.091042453358316,"self_citation_contribution":0.4636563680037475,"citation_network_contribution":0.0,"self_endowment_contribution":0.4636563680037475,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9601,"is_data_producer":false,"deposit_databanks":null,"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":708120,"name":"Paige Dubelko","orcid":null,"position":1,"is_corresponding":false},{"id":230243,"name":"Rebecca Kuan","orcid":"0000-0002-5896-5548","position":2,"is_corresponding":false},{"id":338600,"name":"William D. Chronister","orcid":null,"position":3,"is_corresponding":false},{"id":505509,"name":"Kaylin Muskat","orcid":null,"position":4,"is_corresponding":false},{"id":720459,"name":"Jyotirmoy Das","orcid":"0000-0002-5649-4658","position":5,"is_corresponding":false},{"id":106289,"name":"Elizabeth J. Phillips","orcid":"0000-0002-7623-3383","position":6,"is_corresponding":false},{"id":11900,"name":"S. Mallal","orcid":"0000-0002-7036-1309","position":7,"is_corresponding":false},{"id":110383,"name":"Grégory Seumois","orcid":"0000-0002-8164-6852","position":8,"is_corresponding":false},{"id":110385,"name":"Pandurangan Vijayanand","orcid":"0000-0001-7067-9723","position":9,"is_corresponding":false},{"id":55670,"name":"Alessandro Sette","orcid":"0000-0001-7013-2250","position":10,"is_corresponding":false},{"id":406366,"name":"Maria Lerm","orcid":"0000-0002-5092-9892","position":11,"is_corresponding":false},{"id":34766,"name":"Bjoern Peters","orcid":"0000-0002-8457-6693","position":12,"is_corresponding":false},{"id":230241,"name":"Cecilia S. Lindestam Arlehamn","orcid":"0000-0001-7302-8002","position":13,"is_corresponding":false},{"id":602015,"name":"Akul Singhania","orcid":"0000-0002-6941-3618","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:47:28.018172Z","pmid":"34902786","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":[]}