{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T12:06:47Z","timestamp":1762430807337},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2014,4,9]],"date-time":"2014-04-09T00:00:00Z","timestamp":1397001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"German Federal Ministry of Education and Research"},{"name":"DFG Research Center and Cluster of Excellence \u2013 Center for Regenerative Therapies Dresden","award":["FZ 111"],"award-info":[{"award-number":["FZ 111"]}]},{"name":"NIH\/DFG Research Career Transition Award Program","award":["KO 3418\/1-1"],"award-info":[{"award-number":["KO 3418\/1-1"]}]},{"name":"Das zuckerkranke Kind"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,4,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Autoimmune diabetes is characterized by autoantigen-specific T cell-mediated destruction of pancreatic islet beta cells, and CD8+ T cells are key players during this process. We assessed whether the bitransgenic RIP-CD80 x RIP-LCMV-GP (RIP-CD80GP) mice may be a versatile antigen-specific model of inducible CD8+ T cell-mediated autoimmune diabetes. Antigen-encoding DNA, peptide-loaded dendritic cells and antigen plus incomplete Freund's adjuvant were used for vaccination. Of 14 pancreatic proteins tested by DNA vaccination, murine pre-proinsulin 2 (100% of mice; median time after vaccination, 60 days) and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) (77%, 58 days) could induce diabetes. Vaccination with DNA encoding for zinc transporter 8, Ia-2, Ia-2\u03b2, glutamic acid decarboxylase 67 (Gad67), chromogranin A, insulinoma amyloid polypeptide and homeobox protein Nkx-2.2 induced diabetes development in 25\u201333% of mice. Vaccination with DNA encoding for Gad65, secretogranin 5, pancreas\/duodenum homeobox protein 1 (Pdx1), carboxyl ester lipase, glucagon and control hepatitis B surface antigen (HBsAg) induced diabetes in &amp;lt;20% of mice. Diabetes induction efficiency could be increased by DNA vaccination with a vector encoding a ubiquitin\u2013antigen fusion construct. Diabetic mice had florid T cell islet infiltration. CD8+ T cell targets of IGRP were identified with a peptide library-based enzyme-linked immunospot assay, and diabetes could also be induced by vaccination with major histocompatibility complex (MHC) class I-restricted IGRP peptides loaded on mature dendritic cells. Vaccination with antigen plus incomplete Freund's adjuvant, which can prevent diabetes in other models, led to rapid diabetes development in the RIP-CD80GP mouse. We conclude that RIP-CD80GP mice are a versatile model of antigen specific autoimmune diabetes and may complement existing mouse models of autoimmune diabetes for evaluating CD8+ T cell-targeted prevention strategies.<\/jats:p>","DOI":"10.1111\/cei.12263","type":"journal-article","created":{"date-parts":[[2014,1,6]],"date-time":"2014-01-06T11:07:20Z","timestamp":1389006440000},"page":"199-206","source":"Crossref","is-referenced-by-count":4,"title":["IGRP and insulin vaccination induce CD8+ T cell-mediated autoimmune diabetes in the RIP-CD80GP mouse"],"prefix":"10.1093","volume":"176","author":[{"given":"Y F","family":"Fuchs","sequence":"first","affiliation":[{"name":"DFG \u2013 Center for Regenerative Therapies Dresden (CRTD), Technische Universit\u00e4t Dresden, Dresden, Germany"},{"name":"Paul Langerhans Institute Dresden-German Center for Diabetes Research (DZD), Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Adler","sequence":"additional","affiliation":[{"name":"Forschergruppe Diabetes e.V., Neuherberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Lindner","sequence":"additional","affiliation":[{"name":"DFG \u2013 Center for Regenerative Therapies Dresden (CRTD), Technische Universit\u00e4t Dresden, Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Karasinsky","sequence":"additional","affiliation":[{"name":"DFG \u2013 Center for Regenerative Therapies Dresden (CRTD), Technische Universit\u00e4t Dresden, Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Wilhelm","sequence":"additional","affiliation":[{"name":"DFG \u2013 Center for Regenerative Therapies Dresden (CRTD), Technische Universit\u00e4t Dresden, Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Weigelt","sequence":"additional","affiliation":[{"name":"DFG \u2013 Center for Regenerative Therapies Dresden (CRTD), Technische Universit\u00e4t Dresden, Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Balke","sequence":"additional","affiliation":[{"name":"Institute of Diabetes Research, Helmholtz Zentrum M\u00fcnchen, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universit\u00e4t M\u00fcnchen, Neuherberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"F\u00f6rtsch","sequence":"additional","affiliation":[{"name":"Institute of Diabetes Research, Helmholtz Zentrum M\u00fcnchen, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universit\u00e4t M\u00fcnchen, Neuherberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L F","family":"Mortler-Hildebrandt","sequence":"additional","affiliation":[{"name":"Institute of Diabetes Research, Helmholtz Zentrum M\u00fcnchen, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universit\u00e4t M\u00fcnchen, Neuherberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D M","family":"Harlan","sequence":"additional","affiliation":[{"name":"Diabetes Center of Excellence, University of Massachusetts, Worcester, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Pechhold","sequence":"additional","affiliation":[{"name":"Diabetes Center of Excellence, University of Massachusetts, Worcester, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A-G","family":"Ziegler","sequence":"additional","affiliation":[{"name":"Forschergruppe Diabetes e.V., Neuherberg, Germany"},{"name":"Institute of Diabetes Research, Helmholtz Zentrum M\u00fcnchen, and Forschergruppe Diabetes, Klinikum rechts 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