{"doi":"10.1101/2024.04.06.588414","title":"CAR Tregs mediate linked suppression and infectious tolerance in islet transplantation","abstract":"Abstract Regulatory T cells (Tregs) have potential as a cell-based therapy to prevent or treat transplant rejection and autoimmunity. Using an HLA-A2-specific chimeric antigen receptor (A2-CAR), we previously showed that adoptive transfer of A2-CAR Tregs limited anti-HLA-A2 alloimmunity. However, it was unknown if A2-CAR Tregs could also limit immunity to autoantigens. Using a model of HLA-A2 + islet transplantation into immunodeficient non-obese diabetic mice, we investigated if A2-CAR Tregs could control diabetes induced by islet-autoreactive (BDC2.5) T cells. In mice transplanted with HLA-A2 + islets, A2-CAR Tregs reduced BDC2.5 T cell engraftment, proliferation and cytokine production, and protected mice from diabetes. Tolerance to islets was systemic, including protection of the HLA-A2 negative endogenous pancreas. In tolerant mice, a significant proportion of BDC2.5 T cells gained FOXP3 expression suggesting that long-term tolerance is maintained by de novo Treg generation. Thus, A2-CAR Tregs mediate linked suppression and infectious tolerance and have potential therapeutic use to simultaneously control both allo- and autoimmunity in islet transplantation. One Sentence Summary Alloreactive chimeric antigen receptor-engineered regulatory T cells limit diabetogenic T cell engraftment and function to prevent type 1 diabetes.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":484857,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9478,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1032577,"name":"Vivian Fung","orcid":null,"position":1,"is_corresponding":false},{"id":516084,"name":"Eleanor Y. Chen","orcid":"0000-0003-4372-7560","position":2,"is_corresponding":false},{"id":1326995,"name":"Manjurul Haque","orcid":"0000-0002-9838-0667","position":3,"is_corresponding":false},{"id":1327448,"name":"Jana Gillies","orcid":null,"position":4,"is_corresponding":false},{"id":1031824,"name":"Justin A. Spanier","orcid":"0000-0002-3282-4499","position":5,"is_corresponding":false},{"id":1031827,"name":"Majid Mojibian","orcid":"0000-0002-1595-9068","position":6,"is_corresponding":false},{"id":247528,"name":"Brian T. Fife","orcid":"0000-0001-9826-5637","position":7,"is_corresponding":false},{"id":685436,"name":"Megan K. Levings","orcid":"0000-0002-0305-5790","position":8,"is_corresponding":false},{"id":1031825,"name":"Christine M. Wardell","orcid":"0000-0002-2418-5076","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-19T02:07:42.971417Z","pmid":"38645184","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":[]}