{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T11:02:24Z","timestamp":1788346944650,"version":"build-2803163510"},"reference-count":57,"publisher":"National Academy of Sciences","issue":"6","license":[{"start":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T00:00:00Z","timestamp":1706486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014712","name":"DHAC | NHMRC | National Institute for Dementia Research","doi-asserted-by":"publisher","award":["GNT1150425"],"award-info":[{"award-number":["GNT1150425"]}],"id":[{"id":"10.13039\/501100014712","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,2,6]]},"abstract":"<jats:p>\n                    Persistent antigen exposure results in the differentiation of functionally impaired, also termed exhausted, T cells which are maintained by a distinct population of precursors of exhausted T (T\n                    <jats:sub>PEX<\/jats:sub>\n                    ) cells. T cell exhaustion is well studied in the context of chronic viral infections and cancer, but it is unclear whether and how antigen-driven T cell exhaustion controls progression of autoimmune diabetes and whether this process can be harnessed to prevent diabetes. Using nonobese diabetic (NOD) mice, we show that some CD8+ T cells specific for the islet antigen, islet-specific glucose-6-phosphatase catalytic subunit\u2013related protein (IGRP) displayed terminal exhaustion characteristics within pancreatic islets but were maintained in the T\n                    <jats:sub>PEX<\/jats:sub>\n                    cell state in peripheral lymphoid organs (PLO). More IGRP-specific T cells resided in the PLO than in islets. To examine the impact of extraislet antigen exposure on T cell exhaustion in diabetes, we generated transgenic NOD mice with inducible IGRP expression in peripheral antigen-presenting cells. Antigen exposure in the extraislet environment induced severely exhausted IGRP-specific T cells with reduced ability to produce interferon (IFN)\u03b3, which protected these mice from diabetes. Our data demonstrate that T cell exhaustion induced by delivery of antigen can be harnessed to prevent autoimmune diabetes.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2315419121","type":"journal-article","created":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T15:00:21Z","timestamp":1706540421000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":9,"title":["Extraislet expression of islet antigen boosts T cell exhaustion to partially prevent autoimmune diabetes"],"prefix":"10.1073","volume":"121","author":[{"given":"Claudia","family":"Selck","sequence":"first","affiliation":[{"name":"Immunology and Diabetes Unit, St. Vincent\u2019s Institute, Fitzroy, VIC 3065, Australia"},{"name":"Department of Medicine, St. Vincent\u2019s Hospital, University of Melbourne, Fitzroy, VIC 3065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6187-5783","authenticated-orcid":false,"given":"Gaurang","family":"Jhala","sequence":"additional","affiliation":[{"name":"Immunology and Diabetes Unit, St. Vincent\u2019s Institute, Fitzroy, VIC 3065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7571-680X","authenticated-orcid":false,"given":"David J.","family":"De George","sequence":"additional","affiliation":[{"name":"Immunology and Diabetes Unit, St. Vincent\u2019s Institute, Fitzroy, VIC 3065, Australia"},{"name":"Department of Medicine, St. Vincent\u2019s Hospital, University of Melbourne, Fitzroy, VIC 3065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Ting J.","family":"Kwong","sequence":"additional","affiliation":[{"name":"Immunology and Diabetes Unit, St. Vincent\u2019s Institute, Fitzroy, VIC 3065, Australia"},{"name":"Department of Medicine, St. Vincent\u2019s Hospital, University of Melbourne, Fitzroy, VIC 3065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8450-5780","authenticated-orcid":false,"given":"Marie K.","family":"Christensen","sequence":"additional","affiliation":[{"name":"Immunology and Diabetes Unit, St. Vincent\u2019s Institute, Fitzroy, VIC 3065, Australia"},{"name":"Department of Medicine, St. Vincent\u2019s Hospital, University of Melbourne, Fitzroy, VIC 3065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan G.","family":"Pappas","sequence":"additional","affiliation":[{"name":"Immunology and Diabetes Unit, St. Vincent\u2019s Institute, Fitzroy, VIC 3065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[{"name":"Immunology and Diabetes Unit, St. Vincent\u2019s Institute, Fitzroy, VIC 3065, Australia"},{"name":"Department of Medicine, St. Vincent\u2019s Hospital, University of Melbourne, Fitzroy, VIC 3065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Ge","sequence":"additional","affiliation":[{"name":"Immunology and Diabetes Unit, St. Vincent\u2019s Institute, Fitzroy, VIC 3065, Australia"},{"name":"Department of Medicine, St. Vincent\u2019s Hospital, University of Melbourne, Fitzroy, VIC 3065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prerak","family":"Trivedi","sequence":"additional","affiliation":[{"name":"Immunology and Diabetes Unit, St. Vincent\u2019s Institute, Fitzroy, VIC 3065, Australia"},{"name":"Department of Medicine, St. Vincent\u2019s Hospital, University of Melbourne, Fitzroy, VIC 3065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Kallies","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6604-6640","authenticated-orcid":false,"given":"Helen E.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Immunology and Diabetes Unit, St. Vincent\u2019s Institute, Fitzroy, VIC 3065, Australia"},{"name":"Department of Medicine, St. Vincent\u2019s Hospital, University of Melbourne, Fitzroy, VIC 3065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7273-2556","authenticated-orcid":false,"given":"Thomas W. H.","family":"Kay","sequence":"additional","affiliation":[{"name":"Immunology and Diabetes Unit, St. Vincent\u2019s Institute, Fitzroy, VIC 3065, Australia"},{"name":"Department of Medicine, St. Vincent\u2019s Hospital, University of Melbourne, Fitzroy, VIC 3065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4735-2540","authenticated-orcid":false,"given":"Balasubramanian","family":"Krishnamurthy","sequence":"additional","affiliation":[{"name":"Immunology and Diabetes Unit, St. Vincent\u2019s Institute, Fitzroy, VIC 3065, Australia"},{"name":"Department of Medicine, St. Vincent\u2019s Hospital, University of Melbourne, Fitzroy, VIC 3065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,1,29]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.12.2205"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-041015-055318"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0221-9"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0633-5"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.29.03.06.dc05-1006"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198605223142106"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/1520-7560(200007\/08)16:4<251::AID-DMRR126>3.0.CO;2-C"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature19330"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.07.021"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0223-7"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0312-6"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-022-01210-5"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21109-3"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.583702"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14468"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20022125"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/dme.13762"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.2337\/dbi18-0002"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0932778100"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29602"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2100362"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20192362"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04248-x"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aai7793"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1302100"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.86065"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.11.002"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.10.009"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.97828"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature22367"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-022-01379-9"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000800"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1325-x"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature19317"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.2337\/db09-1129"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-021-05453-z"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1922-8"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-18-0950"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.2337\/db23-0178"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01103"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.2.825"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061462"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0811139106"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature16962"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.03.015"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-00982-6"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc14-2349"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20180684"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.2337\/db09-1400"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.08.002"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.142680"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.161812"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI126595"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20090300"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.10.1663"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201242435"},{"key":"e_1_3_4_57_2","unstructured":"B. Krishnamurthy D. De George Single cell analysis of CD45+ immune cells from the islets of non-obese diabetic (NOD) mice. GEO. http:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?Acc=GSE247956. Deposited 16 November 2023."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2315419121","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T15:02:44Z","timestamp":1706540564000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2315419121"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,29]]},"references-count":57,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,2,6]]}},"alternative-id":["10.1073\/pnas.2315419121"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2315419121","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,29]]},"assertion":[{"value":"2023-09-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2315419121"}}