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B<jats:sup>\u2212\/\u2212<\/jats:sup> mice are also resistant to other spontaneous and experimentally induced autoimmune diseases, including arthritis, systemic lupus erythematosus, <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>j\u00f6gren syndrome and thyroiditis. Under normal conditions, activation of self\u2010reactive T cells in the periphery is limited by <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup>\u00a0<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>25<jats:sup>+<\/jats:sup> natural regulatory T (<jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>reg) cells. B<jats:sup>\u2212\/\u2212<\/jats:sup> <jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content>.<jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>\u20102h4 mice, normally resistant to spontaneous autoimmune thyroiditis (<jats:styled-content style=\"fixed-case\">SAT<\/jats:styled-content>), develop <jats:styled-content style=\"fixed-case\">SAT<\/jats:styled-content> when Treg cells are depleted, suggesting that <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>reg cells are preferentially activated when autoantigen is initially presented by non\u2010B\u2010cell antigen\u2010presenting cells. To test the hypothesis that increased <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>reg cell activity in B<jats:sup>\u2212\/\u2212<\/jats:sup> mice contributes to their resistance to other autoimmune diseases, WT and B<jats:sup>\u2212\/\u2212<\/jats:sup> <jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content> mice were given anti\u2010<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>25 to transiently deplete <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup>\u00a0<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>25<jats:sup>+<\/jats:sup> <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>reg cells. The <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content> and B<jats:sup>\u2212\/\u2212<\/jats:sup> <jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content> mice given anti\u2010<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>25 developed diabetes much earlier than <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content> mice given rat <jats:styled-content style=\"fixed-case\">I<\/jats:styled-content>g<jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>, whereas rat <jats:styled-content style=\"fixed-case\">I<\/jats:styled-content>g<jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>\u2010treated B<jats:sup>\u2212\/\u2212<\/jats:sup> mice did not develop diabetes. <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>reg\u2010cell\u2010depleted mice had increased lymphocyte infiltration of the pancreas, salivary glands and thyroid compared with controls given rat <jats:styled-content style=\"fixed-case\">I<\/jats:styled-content>g<jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>. These results are consistent with the hypothesis that resistance of B\u2010cell\u2010deficient <jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content> mice to several autoimmune diseases is due to the activity of <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>reg cells.<\/jats:p>","DOI":"10.1111\/imm.12065","type":"journal-article","created":{"date-parts":[[2013,1,8]],"date-time":"2013-01-08T22:07:27Z","timestamp":1357682847000},"page":"179-186","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Transient depletion of <scp>CD<\/scp>4<sup>+<\/sup>\u00a0<scp>CD<\/scp>25<sup>+<\/sup> regulatory <scp>T<\/scp> cells results in multiple autoimmune diseases in wild\u2010type and B\u2010cell\u2010deficient <scp>NOD<\/scp> mice"],"prefix":"10.1111","volume":"139","author":[{"given":"Jason S.","family":"Ellis","sequence":"first","affiliation":[{"name":"Department of Medicine University of 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