{"doi":"10.1371/journal.ppat.1009249","title":"The NF-κB regulator Bcl-3 restricts terminal differentiation and promotes memory cell formation of CD8+ T cells during viral infection","abstract":"Bcl-3 is an atypical member of the IκB family that acts in the nucleus to modulate transcription of many NF-κB targets in a highly context-dependent manner. Accordingly, complete Bcl-3-/- mice have diverse defects in both innate and adaptive immune responses; however, direct effects of Bcl-3 action in individual immune cell types have not been clearly defined. Here, we document a cell-autonomous role for Bcl-3 in CD8+ T cell differentiation during the response to lymphocytic choriomeningitis virus infection. Single-cell RNA-seq and flow cytometric analysis of virus-specific Bcl3-/- CD8+ T cells revealed that differentiation was skewed towards terminal effector cells at the expense of memory precursor effector cells (MPECs). Accordingly, Bcl3-/- CD8+ T cells exhibited reduced memory cell formation and a defective recall response. Conversely, Bcl-3-overexpression in transgenic CD8+ T cells enhanced MPEC formation but reduced effector cell differentiation. Together, our results establish Bcl-3 as an autonomous determinant of memory/terminal effector cell balance during CD8+ T cell differentiation in response to acute viral infection. Our results provide proof-of-principle for targeting Bcl-3 pharmacologically to optimize adaptive immune responses to infectious agents, cancer cells, vaccines and other stimuli that induce CD8+ T cell differentiation.","journal":"PLoS Pathogens","year":2021,"id":181807,"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":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9511,"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":299367,"name":"Thomas Ciucci","orcid":"0000-0002-5828-0207","position":1,"is_corresponding":false},{"id":285171,"name":"Hongshan Wang","orcid":"0009-0002-8721-1718","position":2,"is_corresponding":false},{"id":430925,"name":"Wanhu Tang","orcid":"0000-0001-9887-6905","position":3,"is_corresponding":false},{"id":733396,"name":"Estefanı́a Claudio","orcid":null,"position":4,"is_corresponding":false},{"id":86111,"name":"Philip M. Murphy","orcid":"0000-0002-1080-8201","position":5,"is_corresponding":false},{"id":299371,"name":"Rémy Bosselut","orcid":"0000-0003-2033-1790","position":6,"is_corresponding":false},{"id":483367,"name":"Ulrich Siebenlist","orcid":"0000-0002-7424-7992","position":7,"is_corresponding":false},{"id":732912,"name":"Hemant Jaiswal","orcid":"0000-0002-8941-4992","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-18T23:48:05.146883Z","pmid":"33508001","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":[]}