{"doi":"10.1084/jem.20221391","title":"CTLA4 depletes T cell endogenous and trogocytosed B7 ligands via cis-endocytosis","abstract":"CD28 and CTLA4 are T cell coreceptors that competitively engage B7 ligands CD80 and CD86 to control adaptive immune responses. While the role of CTLA4 in restraining CD28 costimulatory signaling is well-established, the mechanism has remained unclear. Here, we report that human T cells acquire antigen-presenting-cell (APC)-derived B7 ligands and major histocompatibility complex (MHC) via trogocytosis through CD28:B7 binding. Acquired MHC and B7 enabled T cells to autostimulate, and this process was limited cell-intrinsically by CTLA4, which depletes B7 ligands trogocytosed or endogenously expressed by T cells through cis-endocytosis. Extending this model to the previously proposed extrinsic function of CTLA4 in human regulatory T cells (Treg), we show that blockade of either CD28 or CTLA4 attenuates Treg-mediated depletion of APC B7, indicating that trogocytosis and CTLA4-mediated cis-endocytosis work together to deplete B7 from APCs. Our study establishes CTLA4 as a cell-intrinsic molecular sink that limits B7 availability on the surface of T cells, with implications for CTLA4-targeted therapy.","journal":"The Journal of Experimental Medicine","year":2023,"id":321183,"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":45,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9499,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1033119,"name":"Preston Dennett","orcid":"0000-0003-2044-4437","position":1,"is_corresponding":false},{"id":1020219,"name":"Jibin Zhang","orcid":"0000-0002-9930-4957","position":2,"is_corresponding":false},{"id":700302,"name":"Alice Sherrard","orcid":"0000-0003-1220-4492","position":3,"is_corresponding":false},{"id":271874,"name":"Yunlong Zhao","orcid":"0000-0002-7392-4824","position":4,"is_corresponding":false},{"id":271873,"name":"Takeya Masubuchi","orcid":"0000-0001-6822-3049","position":5,"is_corresponding":false},{"id":106463,"name":"Jack D. Bui","orcid":"0000-0002-9324-368X","position":6,"is_corresponding":false},{"id":281403,"name":"Xu Chen","orcid":"0000-0001-8926-3090","position":7,"is_corresponding":false},{"id":271880,"name":"Enfu Hui","orcid":"0000-0001-7876-2783","position":8,"is_corresponding":false},{"id":271870,"name":"Xiaozheng Xu","orcid":"0000-0001-6888-4285","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T01:07:32.611759Z","pmid":"37042938","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":[]}