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Previously, we found that a liposome\u2010based antigen\u2010specific immunotherapy encapsulating the CD4<jats:sup>+<\/jats:sup> T\u2010cell islet epitope 2.5<jats:sub>mim<\/jats:sub> together with the nuclear factor\u2010\u03baB inhibitor calcitriol induced regulatory T cells and protected from diabetes in NOD mice. Here we investigated whether the same system delivering IGRP<jats:sub>206\u2013214<\/jats:sub> could induce antigen\u2010specific CD8<jats:sup>+<\/jats:sup> T\u2010cell\u2010targeted immune regulation and delay diabetes. Subcutaneous administration of IGRP<jats:sub>206\u2013214<\/jats:sub>\/calcitriol liposomes transiently activated and expanded IGRP\u2010specific T\u2010cell receptor transgenic 8.3 CD8<jats:sup>+<\/jats:sup> T cells. Liposomal co\u2010delivery of calcitriol was required to optimally suppress endogenous IGRP\u2010specific CD8<jats:sup>+<\/jats:sup> T\u2010cell interferon\u2010\u03b3 production and cytotoxicity. Concordantly, a short course of IGRP<jats:sub>206\u2013214<\/jats:sub>\/calcitriol liposomes delayed diabetes progression and reduced insulitis. However, when IGRP<jats:sub>206\u2013214<\/jats:sub>\/calcitriol liposomes were delivered together with 2.5<jats:sub>mim<\/jats:sub>\/calcitriol liposomes, disease protection was not observed and the regulatory effect of 2.5<jats:sub>mim<\/jats:sub>\/calcitriol liposomes was abrogated. Thus, tolerogenic liposomes that target either a dominant CD8<jats:sup>+<\/jats:sup> or a CD4<jats:sup>+<\/jats:sup> T\u2010cell islet epitope can delay diabetes progression but combining multiple epitopes does not enhance protection.<\/jats:p>","DOI":"10.1111\/imcb.12506","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T22:24:04Z","timestamp":1634768644000},"page":"33-48","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Tolerance induction by liposomes targeting a single CD8 epitope IGRP<sub>206\u2013214<\/sub> in a model of type 1 diabetes is impeded by co\u2010targeting a CD4<sup>+<\/sup> islet epitope"],"prefix":"10.1111","volume":"100","author":[{"given":"Irina","family":"Buckle","sequence":"first","affiliation":[{"name":"The University of Queensland Diamantina Institute The University of Queensland Woolloongabba QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeniffer D","family":"Loaiza Naranjo","sequence":"additional","affiliation":[{"name":"The University of Queensland Diamantina Institute The University of Queensland Woolloongabba QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne\u2010Sophie","family":"Bergot","sequence":"additional","affiliation":[{"name":"The University of Queensland Diamantina Institute The University of Queensland Woolloongabba QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian","family":"Zhang","sequence":"additional","affiliation":[{"name":"The University of Queensland Diamantina Institute The University of Queensland Woolloongabba QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghna","family":"Talekar","sequence":"additional","affiliation":[{"name":"The University of Queensland Diamantina Institute The University of Queensland 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