{"doi":"10.1101/2022.11.23.517693","title":"Immune engineered extracellular vesicles to modulate T cell activation in the context of type 1 diabetes","abstract":"Abstract Extracellular vesicles (EVs) are small, biologically active, cell-secreted vesicles that can affect immune responses through antigen presentation and co-stimulation or co-inhibition. We generated designer EVs to modulate autoreactive T cells in the context of type 1 diabetes by engineering K562 cells to express HLA-A*02 (HLA-A2) alongside co-stimulatory CD80 and/or co-inhibitory PD-L1. EVs presenting HLA-A2 and CD80 activated CD8 + T cells in a dose, antigen, and HLA-specific manner. Adding PD-L1 to these EVs produced an immunoregulatory response, reducing CD8 + T cell activation and cytotoxicity in vitro . EVs alone could not stimulate T cells without antigen presenting cells (APCs), suggesting that EVs act by cross-dressing APCs. EVs lacking CD80 were ineffective at modulating CD8 + T cell activation, suggesting that both peptide-HLA complex and costimulatory molecules are required for EV-mediated immune modulation through APC cross-dressing. These results provide mechanistic insight into the rational design of EVs as a cell-free, yet precision medicine-based approach to immunotherapy that can be tailored to promote antigen-specific immune tolerance or pro-inflammatory responses.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":300636,"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":0.9479,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":356514,"name":"Leeana D. Peters","orcid":"0000-0002-7878-0014","position":1,"is_corresponding":false},{"id":991209,"name":"Thinzar Soe Myint","orcid":"0000-0002-5796-9360","position":2,"is_corresponding":false},{"id":356521,"name":"Todd M. Brusko","orcid":"0000-0003-2878-9296","position":3,"is_corresponding":false},{"id":291776,"name":"Edward A. Phelps","orcid":"0000-0001-8666-805X","position":4,"is_corresponding":false},{"id":665379,"name":"Matthew W. Becker","orcid":"0000-0002-3071-7171","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-19T00:31:53.559757Z","pmid":null,"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":[]}