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Although defects in <jats:styled-content style=\"fixed-case\">CTLA<\/jats:styled-content>\u20104 contribute to abnormal <jats:styled-content style=\"fixed-case\">FOXP<\/jats:styled-content>3<jats:sup>+<\/jats:sup> regulatory T (Treg) cell function in rheumatoid arthritis, its role in autoreactive T cells remains elusive. We studied immunity towards the dominant collagen type <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">CII<\/jats:styled-content>) T\u2010cell epitope in collagen\u2010induced arthritis both in the heterologous setting and in the autologous setting where <jats:styled-content style=\"fixed-case\">CII<\/jats:styled-content> is mutated at position E266D in mouse cartilage. <jats:styled-content style=\"fixed-case\">CTLA<\/jats:styled-content>\u20104 regulated all stages of arthritis, including the chronic phase, and affected the priming of autologous but not heterologous <jats:styled-content style=\"fixed-case\">CII<\/jats:styled-content>\u2010reactive T cells. <jats:styled-content style=\"fixed-case\">CTLA<\/jats:styled-content>\u20104 expression by both conventional T (Tconv) cells and Treg cells was required but while Tconv cell expression was needed to control the priming of naive autoreactive T cells, <jats:styled-content style=\"fixed-case\">CTLA<\/jats:styled-content>\u20104 on Treg cells prevented the inflammatory tissue attack. This identifies a cell\u2010type\u2010specific time window when <jats:styled-content style=\"fixed-case\">CTLA<\/jats:styled-content>\u20104\u2010mediated tolerance is most powerful, which has important implications for clinical therapy with immune modulatory drugs.<\/jats:p>","DOI":"10.1111\/imm.12754","type":"journal-article","created":{"date-parts":[[2017,5,12]],"date-time":"2017-05-12T10:38:52Z","timestamp":1494585532000},"page":"125-137","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["CTLA\u20104 expressed by FOXP3<sup>+<\/sup> regulatory T cells prevents inflammatory tissue attack and not T\u2010cell priming in arthritis"],"prefix":"10.1111","volume":"152","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5250-1534","authenticated-orcid":false,"given":"Katrin","family":"Klocke","sequence":"first","affiliation":[{"name":"Division of Medical Inflammation Research Department of Medical Biochemistry and 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