{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T17:30:14Z","timestamp":1760549414257},"reference-count":41,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2013,8,27]],"date-time":"2013-08-27T00:00:00Z","timestamp":1377561600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:p>The cholera toxin <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content> subunit (<jats:styled-content style=\"fixed-case\">CTB<\/jats:styled-content>) has been used as adjuvant to improve oral vaccine delivery in type 1 diabetes. The effect of <jats:styled-content style=\"fixed-case\">CTB<\/jats:styled-content>\/peptide formulations on <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>g\u2010specific <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup> <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content> cells has remained largely unexplored. Here, using tetramer analysis, we investigated how oral delivery of <jats:styled-content style=\"fixed-case\">CTB<\/jats:styled-content> fused to two <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup> <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\u2010cell epitopes, the <jats:styled-content style=\"fixed-case\">BDC<\/jats:styled-content>\u20102.5 <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\u2010cell 2.5mi mimotope and glutamic acid decarboxylase (<jats:styled-content style=\"fixed-case\">GAD<\/jats:styled-content>) 286\u2013300, affected diabetogenic <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup> <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content> cells in nonobese diabetic (<jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content>) mice. When administered i.p., <jats:styled-content style=\"fixed-case\">CTB<\/jats:styled-content>\u20102.5mi activated 2.5mi<jats:sup>+<\/jats:sup> <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content> cells and following intragastric delivery generated <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>g\u2010specific <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>oxp3<jats:sup>+<\/jats:sup> Treg and <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>h2 cells. While 2.5mi<jats:sup>+<\/jats:sup> and <jats:styled-content style=\"fixed-case\">GAD<\/jats:styled-content>\u2010specific <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content> cells were tolerized in diabetes\u2010resistant <jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content>x<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>6.<jats:italic><jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>oxp3<jats:sup>EGFP<\/jats:sup><\/jats:italic> <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>1 and nonobese resistant (NOR) mice, this did not occur in <jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content> mice. This indicated that <jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content> mice had a recessive genetic resistance to induce oral tolerance to both <jats:styled-content style=\"fixed-case\">CTB<\/jats:styled-content>\u2010fused epitopes. In contrast to <jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content>x<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>6.<jats:italic><jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>oxp3<jats:sup>EGFP<\/jats:sup><\/jats:italic> <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>1 mice, oral treatment in <jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content> mice lead to strong 2.5mi<jats:sup>+<\/jats:sup> <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\u2010cell activation and the sequestration of these cells to the effector\u2010memory pool. Oral treatment of <jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content> mice with <jats:styled-content style=\"fixed-case\">CTB<\/jats:styled-content>\u20102.5mi failed to prevent diabetes. These findings underline the importance of investigating the effect of oral vaccine formulations on diabetogenic <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content> cells as in selected cases they may have counterproductive consequences in human patients.<\/jats:p>","DOI":"10.1002\/eji.201343633","type":"journal-article","created":{"date-parts":[[2013,8,8]],"date-time":"2013-08-08T07:13:03Z","timestamp":1375945983000},"page":"2969-2979","source":"Crossref","is-referenced-by-count":6,"title":["Cholera toxin subunit <scp>B<\/scp> peptide fusion proteins reveal impaired oral tolerance induction in diabetes\u2010prone but not in diabetes\u2010resistant mice"],"prefix":"10.1002","volume":"43","author":[{"given":"Maximiliano","family":"Presa","sequence":"first","affiliation":[{"name":"Department of Physiology and Immunology Faculty of Biology University of Barcelona  Barcelona Spain"},{"name":"The Jackson Laboratory Bar Harbor ME USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela Zarama","family":"Ortiz","sequence":"additional","affiliation":[{"name":"Department of Physiology and Immunology Faculty of Biology University of Barcelona  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nahir","family":"Garabatos","sequence":"additional","affiliation":[{"name":"Department of Physiology and Immunology Faculty of Biology University of Barcelona  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Izquierdo","sequence":"additional","affiliation":[{"name":"Department of Physiology and Immunology Faculty of Biology University of Barcelona  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa I.","family":"Rivas","sequence":"additional","affiliation":[{"name":"Department of Physiology and Immunology Faculty of Biology University of Barcelona  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luc","family":"Teyton","sequence":"additional","affiliation":[{"name":"Department of Immunology The Scripps Research Institute  La Jolla CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Conchi","family":"Mora","sequence":"additional","affiliation":[{"name":"Immunology Unit Department of Experimental Medicine School of Medicine University of Lerida and IRB Lerida  Lerida Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Serreze","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory Bar Harbor ME USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Stratmann","sequence":"additional","affiliation":[{"name":"Department of Physiology and Immunology Faculty of Biology University of Barcelona  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,8,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-008-7496-5"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/414792a"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.08.002"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.48.11.2150"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/jaut.2002.0610"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2010.04.005"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.cji.0000171315.82997.9a"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3083.2003.01248.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.9.4610"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2006.10.039"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1098-934"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-008-0017-y"},{"key":"e_1_2_7_14_1","first-page":"153","article-title":"Cholera toxin \u2013 a foe & a friend","volume":"133","author":"S\u00e1nchez j.","year":"2011","journal-title":"Indian J. 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