{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:40:28Z","timestamp":1792806028191,"version":"4.5.0"},"reference-count":48,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"812","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,8,20]]},"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)\u2013A2-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\u2013HLA-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>","DOI":"10.1126\/scitranslmed.adp6519","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T17:58:12Z","timestamp":1755712692000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":29,"title":["CAR T\n                    <sub>reg<\/sub>\n                    cells mediate linked suppression and infectious tolerance in islet transplantation in mice"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2418-5076","authenticated-orcid":true,"given":"Christine M.","family":"Wardell","sequence":"first","affiliation":[{"name":"BC Children\u2019s Hospital Research Institute, University of British Columbia, Vancouver, BC V5Z 4H4, Canada."},{"name":"Department of Surgery, University of British Columbia, Vancouver, BC V6T 1Z4, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5023-5092","authenticated-orcid":true,"given":"Vivian C. W.","family":"Fung","sequence":"additional","affiliation":[{"name":"BC Children\u2019s Hospital Research Institute, University of British Columbia, Vancouver, BC V5Z 4H4, Canada."},{"name":"Department of Surgery, University of British Columbia, Vancouver, BC V6T 1Z4, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor","family":"Chen","sequence":"additional","affiliation":[{"name":"BC Children\u2019s Hospital Research Institute, University of British Columbia, Vancouver, BC V5Z 4H4, Canada."},{"name":"Department of Surgery, University of British Columbia, Vancouver, BC V6T 1Z4, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9838-0667","authenticated-orcid":true,"given":"Manjurul","family":"Haque","sequence":"additional","affiliation":[{"name":"BC Children\u2019s Hospital Research Institute, University of British Columbia, Vancouver, BC V5Z 4H4, Canada."},{"name":"Department of Surgery, University of British Columbia, Vancouver, BC V6T 1Z4, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1616-6467","authenticated-orcid":true,"given":"David F. H.","family":"Tan","sequence":"additional","affiliation":[{"name":"BC Children\u2019s Hospital Research Institute, University of British Columbia, Vancouver, BC V5Z 4H4, Canada."},{"name":"Department of Surgery, University of British Columbia, Vancouver, BC V6T 1Z4, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Leca","sequence":"additional","affiliation":[{"name":"BC Children\u2019s Hospital Research Institute, University of British Columbia, Vancouver, BC V5Z 4H4, Canada."},{"name":"Department of Surgery, University of British Columbia, Vancouver, BC V6T 1Z4, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Gillies","sequence":"additional","affiliation":[{"name":"BC Children\u2019s Hospital Research Institute, University of British Columbia, Vancouver, BC V5Z 4H4, Canada."},{"name":"Department of Surgery, University of British Columbia, Vancouver, BC V6T 1Z4, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3282-4499","authenticated-orcid":true,"given":"Justin A.","family":"Spanier","sequence":"additional","affiliation":[{"name":"Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"Center for Autoimmune Disease Research, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"Department of Medicine, Division of Rheumatic and Autoimmune Diseases, University of Minnesota Medical School, Minneapolis, MN 55455, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1595-9068","authenticated-orcid":true,"given":"Majid","family":"Mojibian","sequence":"additional","affiliation":[{"name":"BC Children\u2019s Hospital Research Institute, University of British Columbia, Vancouver, BC V5Z 4H4, Canada."},{"name":"Department of Surgery, University of British Columbia, Vancouver, BC V6T 1Z4, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9826-5637","authenticated-orcid":true,"given":"Brian T.","family":"Fife","sequence":"additional","affiliation":[{"name":"Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"Center for Autoimmune Disease Research, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"Department of Medicine, Division of Rheumatic and Autoimmune Diseases, University of Minnesota Medical School, Minneapolis, MN 55455, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0305-5790","authenticated-orcid":true,"given":"Megan K.","family":"Levings","sequence":"additional","affiliation":[{"name":"BC Children\u2019s Hospital Research Institute, University of British Columbia, Vancouver, BC V5Z 4H4, Canada."},{"name":"Department of Surgery, University of British Columbia, Vancouver, BC V6T 1Z4, Canada."},{"name":"School of Biomedical Engineering, University of British Columbia, Vancouver, BC V6T 1Z4, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1166135"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.1081644"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-023-06076-2"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0041-4"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00043"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abo2628"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajt.2023.06.012"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.12433"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.15787"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI82771"},{"key":"e_1_3_2_12_2","first-page":"e123672","article-title":"Systematic testing and specificity mapping of alloantigen-specific chimeric antigen receptors in regulatory T cells","volume":"4","author":"Dawson N. 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