{"doi":"10.1126/scitranslmed.adp6519","title":"CAR T\n            <sub>reg</sub>\n            cells mediate linked suppression and infectious tolerance in islet transplantation in mice","abstract":"<jats:p>\n            Regulatory T cells (T\n            <jats:sub>reg</jats:sub>\n            cells) have potential as a cell-based therapy to prevent or treat transplant rejection and autoimmunity. Using a human leukocyte antigen (HLA)–A2-specific chimeric antigen receptor (A2-CAR), we previously showed that adoptive transfer of A2-CAR T\n            <jats:sub>reg</jats:sub>\n            cells can limit anti–HLA-A2 alloimmunity. However, it was unknown whether A2-CAR T\n            <jats:sub>reg</jats:sub>\n            cells could also limit immunity to autoantigens. Using a model of HLA-A2\n            <jats:sup>+</jats:sup>\n            islet transplantation into immunodeficient nonobese diabetic mice, we investigated whether A2-CAR T\n            <jats:sub>reg</jats:sub>\n            cells could control hyperglycemia induced by diabetogenic BDC2.5 effector T cells. In mice transplanted with HLA-A2\n            <jats:sup>+</jats:sup>\n            islets, A2-CAR T\n            <jats:sub>reg</jats:sub>\n            cells reduced BDC2.5 T cell engraftment, proliferation, and cytokine production and protected mice from diabetes. Islet tolerance was systemic, including protection of the HLA-A2\n            <jats:sup>negative</jats:sup>\n            endogenous pancreas. Treated mice remained euglycemic even after removal of the HLA-A2\n            <jats:sup>+</jats:sup>\n            islet graft and A2-CAR T\n            <jats:sub>reg</jats:sub>\n            cells. Thus, A2-CAR T\n            <jats:sub>reg</jats:sub>\n            cells can induce linked suppression and long-lasting tolerance to a distinct autoimmune antigen. Tolerance to the autoantigen does not require A2-CAR T\n            <jats:sub>reg</jats:sub>\n            persistence, indicating the presence of infectious tolerance. Overall, these data demonstrate that A2-CAR T\n            <jats:sub>reg</jats:sub>\n            cells have potential therapeutic use to simultaneously control both allo- and autoimmunity in islet transplantation.\n          </jats:p>","journal":"Science Translational Medicine","year":2025,"id":622778,"datarank":0.48283137373023016,"base_score":3.2188758248682006,"endowment":3.2188758248682006,"self_citation_contribution":0.48283137373023016,"citation_network_contribution":0.0,"self_endowment_contribution":0.48283137373023016,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1609295,"name":"Vivian C. W. Fung","orcid":"0000-0001-5023-5092","position":1,"is_corresponding":false},{"id":1609296,"name":"Eleanor Chen","orcid":null,"position":2,"is_corresponding":false},{"id":1326995,"name":"Manjurul Haque","orcid":"0000-0002-9838-0667","position":3,"is_corresponding":false},{"id":1609298,"name":"David F. H. Tan","orcid":"0009-0004-1616-6467","position":4,"is_corresponding":false},{"id":1609299,"name":"Monica Leca","orcid":null,"position":5,"is_corresponding":false},{"id":1327448,"name":"Jana Gillies","orcid":null,"position":6,"is_corresponding":false},{"id":1031824,"name":"Justin A. Spanier","orcid":"0000-0002-3282-4499","position":7,"is_corresponding":false},{"id":1031827,"name":"Majid Mojibian","orcid":"0000-0002-1595-9068","position":8,"is_corresponding":false},{"id":247528,"name":"Brian T. Fife","orcid":"0000-0001-9826-5637","position":9,"is_corresponding":false},{"id":685436,"name":"Megan K. Levings","orcid":"0000-0002-0305-5790","position":10,"is_corresponding":false},{"id":1031825,"name":"Christine M. Wardell","orcid":"0000-0002-2418-5076","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"CAR T\n            <sub>reg</sub>\n            cells mediate linked suppression and infectious tolerance in islet transplantation in mice","abstract":"<jats:p>\n            Regulatory T cells (T\n            <jats:sub>reg</jats:sub>\n            cells) have potential as a cell-based therapy to prevent or treat transplant rejection and autoimmunity. Using a human leukocyte antigen (HLA)–A2-specific chimeric antigen receptor (A2-CAR), we previously showed that adoptive transfer of A2-CAR T\n            <jats:sub>reg</jats:sub>\n            cells can limit anti–HLA-A2 alloimmunity. However, it was unknown whether A2-CAR T\n            <jats:sub>reg</jats:sub>\n            cells could also limit immunity to autoantigens. Using a model of HLA-A2\n            <jats:sup>+</jats:sup>\n            islet transplantation into immunodeficient nonobese diabetic mice, we investigated whether A2-CAR T\n            <jats:sub>reg</jats:sub>\n            cells could control hyperglycemia induced by diabetogenic BDC2.5 effector T cells. In mice transplanted with HLA-A2\n            <jats:sup>+</jats:sup>\n            islets, A2-CAR T\n            <jats:sub>reg</jats:sub>\n            cells reduced BDC2.5 T cell engraftment, proliferation, and cytokine production and protected mice from diabetes. Islet tolerance was systemic, including protection of the HLA-A2\n            <jats:sup>negative</jats:sup>\n            endogenous pancreas. Treated mice remained euglycemic even after removal of the HLA-A2\n            <jats:sup>+</jats:sup>\n            islet graft and A2-CAR T\n            <jats:sub>reg</jats:sub>\n            cells. Thus, A2-CAR T\n            <jats:sub>reg</jats:sub>\n            cells can induce linked suppression and long-lasting tolerance to a distinct autoimmune antigen. Tolerance to the autoantigen does not require A2-CAR T\n            <jats:sub>reg</jats:sub>\n            persistence, indicating the presence of infectious tolerance. Overall, these data demonstrate that A2-CAR T\n            <jats:sub>reg</jats:sub>\n            cells have potential therapeutic use to simultaneously control both allo- and autoimmunity in islet transplantation.\n          </jats:p>","is_dataset_classified":null,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40834104","pmcid":null,"openalex_id":"https://openalex.org/W4413349976","authors":[],"funders":[],"total_grants":0,"fwci":11.557,"citation_percentile":0.99014298,"influential_citations":0,"citation_trend":[{"year":2025,"count":11},{"year":2026,"count":12}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://www.science.org/doi/pdf/10.1126/scitranslmed.adp6519","host_type":"publisher"},{"url":"https://doi.org/10.1126/scitranslmed.adp6519","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40834104","host_type":"repository"}],"fields_of_study":["CAR-T cell therapy research","Immune Cell Function and Interaction","T-cell and B-cell Immunology","Animals","Islets of Langerhans Transplantation","T-Lymphocytes, Regulatory","Mice, Inbred NOD","Immune Tolerance","Receptors, Chimeric Antigen","Mice","HLA-A2 Antigen","Humans","Autoantigens","Diabetes Mellitus, Experimental"],"mesh_terms":["Receptors, Chimeric Antigen","Animals","Autoantigens","Diabetes Mellitus, Experimental","Humans","Immune Tolerance","HLA-A2 Antigen","Islets of Langerhans Transplantation","Mice, Inbred NOD","T-Lymphocytes, Regulatory","Mice"],"keywords":["Alloimmunity","Immunology","Autoimmunity","Islet","Transplantation","Biology","Adoptive cell transfer","Antigen","Immune system","T cell","Medicine","Diabetes mellitus","Endocrinology","Internal medicine"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T20:59:23.791711Z","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":[]}