{"doi":"10.1016/j.celrep.2025.116184","title":"CD226 identifies effector CD8+ T cells during tuberculosis and costimulates recognition of Mycobacterium tuberculosis-infected macrophages","abstract":"CD8 + T cells defend against Mycobacterium tuberculosis (Mtb) infection but variably recognize Mtb-infected macrophages. To investigate how chronic infection affects the diversity of lung parenchymal CD8 + T cells, we perform single-cell RNA sequencing (scRNA-seq) on cells from C57BL/6J mice infected for 6 and 41 weeks. We identify an effector lineage, including a cluster that expresses high levels of cytotoxic effectors and cytokines, and a dysfunctional lineage that transcriptionally resembles exhausted T cells. The most significantly differentially expressed gene between two distinct CD8 + T cell lineages is Cd226 . Mtb-infected interferon (IFN)γ-enhanced yellow fluorescent protein (EYFP) reporter mice reveal that IFNγ production is enriched in CD226 + CD8 + T cells, confirming these as functional T cells in vivo . Purified CD226 + but not CD226 – CD8 + T cells recognize Mtb-infected macrophages, and CD226 blockade inhibits IFNγ and granzyme B production. Thus, efficient CD8 + T cell recognition of Mtb-infected macrophages requires CD226 costimulation, and CD226 expression identifies CD8 + T cells that recognize Mtb-infected macrophages.","journal":"Cell Reports","year":2025,"id":526696,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9486,"is_data_producer":false,"deposit_databanks":null,"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":970227,"name":"Evelyn Chang","orcid":"0000-0002-3685-6746","position":1,"is_corresponding":false},{"id":649996,"name":"Tasfia Rakib","orcid":"0000-0002-4581-2059","position":2,"is_corresponding":false},{"id":626651,"name":"Kelly Cavallo","orcid":null,"position":3,"is_corresponding":false},{"id":993357,"name":"Rocky Lai","orcid":"0000-0002-3394-3086","position":4,"is_corresponding":false},{"id":297254,"name":"Samuel M. Behar","orcid":"0000-0002-3374-6699","position":5,"is_corresponding":false},{"id":586417,"name":"Tomoyo Shinkawa","orcid":null,"position":0,"is_corresponding":true}],"reference_count":93,"raw_metadata":null,"created_at":"2026-07-19T02:50:34.851930Z","pmid":"40886314","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":[]}