{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:56:10Z","timestamp":1790283370309,"version":"4.1.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T00:00:00Z","timestamp":1712534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100000925","name":"DHAC | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1150425"],"award-info":[{"award-number":["1150425"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Chronic destruction of insulin-producing pancreatic \u03b2 cells by T cells results in autoimmune diabetes. Similar to other chronic T cell\u2013mediated pathologies, a role for T cell exhaustion has been identified in diabetes in humans and NOD mice. The development and differentiation of exhausted T cells depends on exposure to Ag. In this study, we manipulated \u03b2 cell Ag presentation to target exhausted autoreactive T cells by inhibiting IFN-\u03b3\u2013mediated MHC class I upregulation or by ectopically expressing the \u03b2 cell Ag IGRP under the MHC class II promotor in the NOD8.3 model. Islet PD-1+TIM3+CD8+ (terminally exhausted [TEX]) cells were primary producers of islet granzyme B and CD107a, suggestive of cells that have entered the exhaustion program yet maintained cytotoxic capacity. Loss of IFN-\u03b3\u2013mediated \u03b2 cell MHC class I upregulation correlated with a significant reduction in islet TEX cells and diabetes protection in NOD8.3 mice. In NOD.TII\/8.3 mice with IGRP expression induced in APCs, IGRP-reactive T cells remained exposed to high levels of IGRP in the islets and periphery. Consequently, functionally exhausted TEX cells, with reduced granzyme B expression, were significantly increased in these mice and this correlated with diabetes protection. These results indicate that intermediate Ag exposure in wild-type NOD8.3 islets allows T cells to enter the exhaustion program without becoming functionally exhausted. Moreover, Ag exposure can be manipulated to target this key cytotoxic population either by limiting the generation of cytotoxic TIM3+ cells or by driving their functional exhaustion, with both resulting in diabetes protection.<\/jats:p>","DOI":"10.4049\/jimmunol.2300785","type":"journal-article","created":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T12:15:28Z","timestamp":1712578528000},"page":"1658-1669","source":"Crossref","is-referenced-by-count":5,"title":["Altering \u03b2 Cell Antigen Exposure to Exhausted CD8+ T Cells Prevents Autoimmune Diabetes in Mice"],"prefix":"10.1093","volume":"212","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7571-680X","authenticated-orcid":false,"given":"David J","family":"De George","sequence":"first","affiliation":[{"name":"Immunology and Diabetes Unit, St Vincent\u2019s Institute , Fitzroy, Victoria ,","place":["Australia"]},{"name":"Department of Medicine, St Vincent\u2019s Hospital, University of Melbourne , Fitzroy, Victoria ,","place":["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, Victoria ,","place":["Australia"]},{"name":"Department of Medicine, St Vincent\u2019s Hospital, University of Melbourne , Fitzroy, Victoria ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Selck","sequence":"additional","affiliation":[{"name":"Immunology and Diabetes Unit, St Vincent\u2019s Institute , Fitzroy, Victoria ,","place":["Australia"]},{"name":"Department of Medicine, St Vincent\u2019s Hospital, University of Melbourne , Fitzroy, Victoria ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prerak","family":"Trivedi","sequence":"additional","affiliation":[{"name":"Immunology and Diabetes Unit, St Vincent\u2019s Institute , Fitzroy, Victoria ,","place":["Australia"]},{"name":"Department of Medicine, St Vincent\u2019s Hospital, University of Melbourne , Fitzroy, Victoria ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2294-315X","authenticated-orcid":false,"given":"Thomas C","family":"Brodnicki","sequence":"additional","affiliation":[{"name":"Immunology and Diabetes Unit, St Vincent\u2019s Institute , Fitzroy, Victoria ,","place":["Australia"]},{"name":"Department of Medicine, St Vincent\u2019s Hospital, University of Melbourne , Fitzroy, Victoria ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2124-9193","authenticated-orcid":false,"given":"Leanne","family":"Mackin","sequence":"additional","affiliation":[{"name":"Immunology and Diabetes Unit, St Vincent\u2019s Institute , Fitzroy, Victoria ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas W","family":"Kay","sequence":"additional","affiliation":[{"name":"Immunology and Diabetes Unit, St Vincent\u2019s Institute , Fitzroy, Victoria ,","place":["Australia"]},{"name":"Department of Medicine, St Vincent\u2019s Hospital, University of Melbourne , Fitzroy, Victoria ,","place":["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, Victoria ,","place":["Australia"]},{"name":"Department of Medicine, St Vincent\u2019s Hospital, University of Melbourne , Fitzroy, Victoria ,","place":["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, Victoria ,","place":["Australia"]},{"name":"Department of Medicine, St Vincent\u2019s Hospital, University of Melbourne , Fitzroy, Victoria ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,4,8]]},"reference":[{"key":"2025020405505291100_r1","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.humimm.2008.06.008","article-title":"Cytotoxic T-lymphocyte-mediated killing of human pancreatic islet cells in vitro","volume":"69","author":"Campbell","year":"2008","journal-title":"Hum. Immunol."},{"key":"2025020405505291100_r2","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1038\/icb.2015.89","article-title":"Perforin facilitates beta cell killing and regulates autoreactive CD8+ T-cell responses to antigen in mouse models of type 1 diabetes","volume":"94","author":"Trivedi","year":"2016","journal-title":"Immunol. Cell Biol."},{"key":"2025020405505291100_r3","doi-asserted-by":"crossref","first-page":"205","DOI":"10.2337\/db12-0315","article-title":"Human \u03b2-cell killing by autoreactive preproinsulin-specific CD8 T cells is predominantly granule-mediated with the potency dependent upon T-cell receptor avidity","volume":"62","author":"Knight","year":"2013","journal-title":"Diabetes"},{"key":"2025020405505291100_r4","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/0891-6632(88)90002-5","article-title":"Type I diabetes as a chronic autoimmune disease","volume":"2","author":"Eisenbarth","year":"1988","journal-title":"J. Diabet. Complications"},{"key":"2025020405505291100_r5","doi-asserted-by":"crossref","first-page":"e202201503","DOI":"10.26508\/lsa.202201503","article-title":"Autoreactive CD8 T cells in NOD mice exhibit phenotypic heterogeneity but restricted TCR gene usage","volume":"5","author":"Kasmani","year":"2022","journal-title":"Life Sci. Alliance"},{"key":"2025020405505291100_r6","doi-asserted-by":"crossref","first-page":"e20192362","DOI":"10.1084\/jem.20192362","article-title":"Single-cell RNA sequencing of murine islets shows high cellular complexity at all stages of autoimmune diabetes","volume":"217","author":"Zakharov","year":"2020","journal-title":"J. Exp. Med."},{"key":"2025020405505291100_r7","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1146\/annurev-immunol-041015-055318","article-title":"CD8 T cell exhaustion during chronic viral infection and cancer","volume":"37","author":"McLane","year":"2019","journal-title":"Annu. Rev. Immunol."},{"key":"2025020405505291100_r8","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/s41586-021-04248-x","article-title":"An autoimmune stem-like CD8 T cell population drives type 1 diabetes","volume":"602","author":"Gearty","year":"2022","journal-title":"Nature"},{"key":"2025020405505291100_r9","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.4049\/jimmunol.2100362","article-title":"Self-renewing islet TCF1+ CD8 T cells undergo IL-27-controlled differentiation to become TCF1\u2212 terminal effectors during the progression of type 1 diabetes","volume":"207","author":"Ciecko","year":"2021","journal-title":"J. Immunol."},{"key":"2025020405505291100_r10","doi-asserted-by":"crossref","first-page":"e2315419121","DOI":"10.1073\/pnas.2315419121","article-title":"Extraislet expression of islet antigen boosts T cell exhaustion to partially prevent autoimmune diabetes","volume":"121","author":"Selck","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025020405505291100_r11","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.immuni.2020.04.019","article-title":"Charting the roadmap of T cell exhaustion","volume":"52","author":"Chu","year":"2020","journal-title":"Immunity"},{"key":"2025020405505291100_r12","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/s41467-023-35948-9","article-title":"IFN\u03b3 signaling in cytotoxic T cells restricts anti-tumor responses by inhibiting the maintenance and diversity of intra-tumoral stem-like T cells","volume":"14","author":"Mazet","year":"2023","journal-title":"Nat. Commun."},{"key":"2025020405505291100_r13","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.immuni.2022.01.018","article-title":"Tfh-cell-derived interleukin 21 sustains effector CD8+ T cell responses during chronic viral infection","volume":"55","author":"Zander","year":"2022","journal-title":"Immunity"},{"key":"2025020405505291100_r14","doi-asserted-by":"crossref","first-page":"E5444","DOI":"10.1073\/pnas.1604256113","article-title":"IL2R\u03b2-dependent signals drive terminal exhaustion and suppress memory development during chronic viral infection","volume":"113","author":"Beltra","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025020405505291100_r15","doi-asserted-by":"crossref","first-page":"e1425","DOI":"10.1002\/cti2.1425","article-title":"Diabetes induced by checkpoint inhibition in nonobese diabetic mice can be prevented or reversed by a JAK1\/JAK2 inhibitor","volume":"11","author":"Ge","year":"2022","journal-title":"Clin. Transl. Immunology"},{"key":"2025020405505291100_r16","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1084\/jem.20022125","article-title":"The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice","volume":"198","author":"Ansari","year":"2003","journal-title":"J. Exp. Med."},{"key":"2025020405505291100_r17","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1084\/jem.186.10.1663","article-title":"Spontaneous autoimmune diabetes in monoclonal T cell nonobese diabetic mice","volume":"186","author":"Verdaguer","year":"1997","journal-title":"J. Exp. Med."},{"key":"2025020405505291100_r18","doi-asserted-by":"crossref","first-page":"110747","DOI":"10.1016\/j.celrep.2022.110747","article-title":"Interferons limit autoantigen-specific CD8+ T-cell expansion in the non-obese diabetic mouse","volume":"39","author":"Jhala","year":"2022","journal-title":"Cell Rep."},{"key":"2025020405505291100_r19","doi-asserted-by":"crossref","first-page":"5714","DOI":"10.4049\/jimmunol.172.9.5714","article-title":"Suppressor of cytokine signaling-1 overexpression protects pancreatic \u03b2 cells from CD8+ T cell-mediated autoimmune destruction","volume":"172","author":"Chong","year":"2004","journal-title":"J. Immunol."},{"key":"2025020405505291100_r20","doi-asserted-by":"crossref","first-page":"3258","DOI":"10.1172\/JCI29602","article-title":"Responses against islet antigens in NOD mice are prevented by tolerance to proinsulin but not IGRP","volume":"116","author":"Krishnamurthy","year":"2006","journal-title":"J. Clin. Invest."},{"key":"2025020405505291100_r21","doi-asserted-by":"crossref","first-page":"e86065","DOI":"10.1172\/jci.insight.86065","article-title":"Perinatal tolerance to proinsulin is sufficient to prevent autoimmune diabetes","volume":"1","author":"Jhala","year":"2016","journal-title":"JCI Insight"},{"key":"2025020405505291100_r22","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.1084\/jem.20121015","article-title":"Programmed death 1 protects from fatal circulatory failure during systemic virus infection of mice","volume":"209","author":"Frebel","year":"2012","journal-title":"J. Exp. Med."},{"key":"2025020405505291100_r23","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41586-019-1326-9","article-title":"TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection","volume":"571","author":"Alfei","year":"2019","journal-title":"Nature"},{"key":"2025020405505291100_r24","doi-asserted-by":"crossref","first-page":"e1840","DOI":"10.21769\/BioProtoc.1840","article-title":"Isolation and culture of the islets of Langerhans from mouse pancreas","volume":"6","author":"Graham","year":"2016","journal-title":"Bio-protocol"},{"key":"2025020405505291100_r25","doi-asserted-by":"crossref","first-page":"6292","DOI":"10.4049\/jimmunol.170.12.6292","article-title":"Fas is detectable on \u03b2 cells in accelerated, but not spontaneous, diabetes in nonobese diabetic mice","volume":"170","author":"Darwiche","year":"2003","journal-title":"J. Immunol."},{"key":"2025020405505291100_r26","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/978-1-4939-2522-3_12","article-title":"Measuring death of pancreatic beta cells in response to stress and cytotoxic T cells","volume":"1292","author":"Wali","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"2025020405505291100_r27","doi-asserted-by":"crossref","first-page":"4726","DOI":"10.4049\/jimmunol.157.10.4726","article-title":"Acceleration of spontaneous diabetes in TCR-beta-transgenic nonobese diabetic mice by beta-cell cytotoxic CD8+ T cells expressing identical endogenous TCR-alpha chains","volume":"157","author":"Verdaguer","year":"1996","journal-title":"J Immunol"},{"key":"2025020405505291100_r28","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nature19330","article-title":"Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy","volume":"537","author":"Im","year":"2016","journal-title":"Nature"},{"key":"2025020405505291100_r29","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.2337\/db09-1129","article-title":"Prevention of diabetes by FTY720-mediated stabilization of peri-islet tertiary lymphoid organs","volume":"59","author":"Penaranda","year":"2010","journal-title":"Diabetes"},{"key":"2025020405505291100_r30","doi-asserted-by":"crossref","first-page":"2987","DOI":"10.3389\/fimmu.2018.02987","article-title":"Regulation of effector and memory CD8 T cell differentiation by IL-2-A balancing act","volume":"9","author":"Kalia","year":"2018","journal-title":"Front. Immunol."},{"key":"2025020405505291100_r31","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0022-1759(03)00265-5","article-title":"Sensitive and viable identification of antigen-specific CD8+ T cells by a flow cytometric assay for degranulation","volume":"281","author":"Betts","year":"2003","journal-title":"J. Immunol. Methods"},{"key":"2025020405505291100_r32","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1172\/JCI2899","article-title":"IFN-gamma action on pancreatic beta cells causes class I MHC upregulation but not diabetes","volume":"102","author":"Thomas","year":"1998","journal-title":"J. Clin. Invest."},{"key":"2025020405505291100_r33","doi-asserted-by":"crossref","first-page":"31319","DOI":"10.1073\/pnas.2019743117","article-title":"Cytocidal macrophages in symbiosis with CD4 and CD8 T cells cause acute diabetes following checkpoint blockade of PD-1 in NOD mice","volume":"117","author":"Hu","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025020405505291100_r34","doi-asserted-by":"crossref","first-page":"1117092","DOI":"10.3389\/fimmu.2023.1117092","article-title":"IL-15 promotes self-renewal of progenitor exhausted CD8 T cells during persistent antigenic stimulation","volume":"14","author":"Lee","year":"2023","journal-title":"Front. Immunol."},{"key":"2025020405505291100_r35","doi-asserted-by":"crossref","first-page":"16004","DOI":"10.1073\/pnas.0407192101","article-title":"Antigen-independent memory CD8 T cells do not develop during chronic viral infection","volume":"101","author":"Wherry","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025020405505291100_r36","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/j.immuni.2019.11.002","article-title":"Proliferating transitory T cells with an effector-like transcriptional signature emerge from PD-1+ stem-like CD8+ T cells during chronic infection","volume":"51","author":"Hudson","year":"2019","journal-title":"Immunity"},{"key":"2025020405505291100_r37","doi-asserted-by":"crossref","first-page":"425","DOI":"10.2337\/db11-0948","article-title":"Complete diabetes protection despite delayed thymic tolerance in NOD8.3 TCR transgenic mice due to antigen-induced extrathymic deletion of T cells","volume":"61","author":"Krishnamurthy","year":"2012","journal-title":"Diabetes"},{"key":"2025020405505291100_r38","doi-asserted-by":"crossref","first-page":"8623","DOI":"10.1073\/pnas.0809818106","article-title":"High antigen levels are the cause of T cell exhaustion during chronic viral infection","volume":"106","author":"Mueller","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025020405505291100_r39","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/cei.13424","article-title":"Immune checkpoint inhibitor diabetes mellitus: a novel form of autoimmune diabetes","volume":"200","author":"Quandt","year":"2020","journal-title":"Clin. Exp. Immunol."},{"key":"2025020405505291100_r40","doi-asserted-by":"crossref","first-page":"eaai7793","DOI":"10.1126\/sciimmunol.aai7793","article-title":"Partial exhaustion of CD8 T cells and clinical response to teplizumab in new-onset type 1 diabetes","volume":"1","author":"Long","year":"2016","journal-title":"Sci. Immunol."},{"key":"2025020405505291100_r41","doi-asserted-by":"crossref","first-page":"e142680","DOI":"10.1172\/jci.insight.142680","article-title":"Exhausted-like CD8+ T cell phenotypes linked to C-peptide preservation in alefacept-treated T1D subjects","volume":"6","author":"Diggins","year":"2021","journal-title":"JCI Insight"},{"key":"2025020405505291100_r42","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1111\/imm.12729","article-title":"Anti-CD3 treatment up-regulates programmed cell death protein-1 expression on activated effector T cells and severely impairs their inflammatory capacity","volume":"151","author":"Wallberg","year":"2017","journal-title":"Immunology"},{"key":"2025020405505291100_r43","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1038\/s41590-019-0312-6","article-title":"Subsets of exhausted CD8+ T cells differentially mediate tumor control and respond to checkpoint blockade","volume":"20","author":"Miller","year":"2019","journal-title":"Nat. Immunol."},{"key":"2025020405505291100_r44","doi-asserted-by":"crossref","first-page":"eadc9346","DOI":"10.1126\/sciadv.adc9346","article-title":"Kr\u00fcppel-like factor 4 regulates the cytolytic effector function of exhausted CD8 T cells","volume":"8","author":"Nah","year":"2022","journal-title":"Sci. Adv."},{"key":"2025020405505291100_r45","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1126\/science.283.5403.857","article-title":"Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes","volume":"283","author":"Schmitz","year":"1999","journal-title":"Science"},{"key":"2025020405505291100_r46","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1084\/jem.189.6.991","article-title":"Dramatic rise in plasma viremia after CD8+ T cell depletion in simian immunodeficiency virus-infected macaques","volume":"189","author":"Jin","year":"1999","journal-title":"J. Exp. Med."},{"key":"2025020405505291100_r47","doi-asserted-by":"crossref","first-page":"6688","DOI":"10.1073\/pnas.1131954100","article-title":"Beta cell MHC class I is a late requirement for diabetes","volume":"100","author":"Hamilton-Williams","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025020405505291100_r48","doi-asserted-by":"crossref","first-page":"812","DOI":"10.2337\/diab.45.6.812","article-title":"Genetic absence of \u03b3-interferon delays but does not prevent diabetes in NOD mice","volume":"45","author":"Hultgren","year":"1996","journal-title":"Diabetes"},{"key":"2025020405505291100_r49","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.2337\/diabetes.49.12.2007","article-title":"Interferon-gamma receptor signaling is dispensable in the development of autoimmune type 1 diabetes in NOD mice","volume":"49","author":"Serreze","year":"2000","journal-title":"Diabetes"},{"key":"2025020405505291100_r50","doi-asserted-by":"crossref","first-page":"710","DOI":"10.2337\/db16-0846","article-title":"Interferon-\u03b3 limits diabetogenic CD8+ T-cell effector responses in type 1 diabetes","volume":"66","author":"Driver","year":"2017","journal-title":"Diabetes"},{"key":"2025020405505291100_r51","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1006\/jaut.2002.0604","article-title":"Gamma interferon paradoxically inhibits the development of diabetes in the NOD mouse","volume":"19","author":"Sobel","year":"2002","journal-title":"Journal of Autoimmunity"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/212\/11\/1658\/61476382\/ji2300785.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/212\/11\/1658\/61476382\/ji2300785.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T05:53:57Z","timestamp":1738648437000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/212\/11\/1658\/7926118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,8]]},"references-count":51,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,6,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.2300785","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,6]]},"published":{"date-parts":[[2024,4,8]]}}}