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The patients also have a functional defect in the <jats:styled-content style=\"fixed-case\">FOXP<\/jats:styled-content>3<jats:sup>+<\/jats:sup> regulatory T cell population, but its origin is unclear. Here, we have used T cell receptor sequencing to analyse the clonal relationship of major <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup> T cell subsets in three patients and three healthy controls. The naive regulatory T cells showed little overlap with helper T cell subsets, supporting divergence in the thymus. The activated\/memory regulatory T cell subset displayed more sharing with helper T cells, but was mainly recruited from the naive regulatory T cell population. These clonal patterns were very similar in both patients and controls. However, naive regulatory T cells isolated from the patients had a significantly longer T cell receptor complementarity\u2010determining region 3 than any other population, suggesting failure of thymic selection. These data indicate that the peripheral differentiation of regulatory T cells in <jats:styled-content style=\"fixed-case\">APS<\/jats:styled-content>\u20101 patients is not different from that in healthy controls. Rather, the patients' naive regulatory T cells may have an intrinsic defect imprinted already in the thymus.<\/jats:p>","DOI":"10.1111\/sji.12586","type":"journal-article","created":{"date-parts":[[2017,7,22]],"date-time":"2017-07-22T12:56:35Z","timestamp":1500728195000},"page":"221-228","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Clonal Analysis of Regulatory T Cell Defect in Patients with Autoimmune Polyendocrine Syndrome Type 1 Suggests Intrathymic Impairment"],"prefix":"10.1111","volume":"86","author":[{"given":"T.\u2010T.","family":"Koivula","sequence":"first","affiliation":[{"name":"Department of Bacteriology and Immunology University of Helsinki Helsinki Finland"},{"name":"Research Programs Unit Immunobiology University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. M.","family":"Laakso","sequence":"additional","affiliation":[{"name":"Department of Bacteriology and Immunology University of Helsinki Helsinki Finland"},{"name":"Research Programs Unit Immunobiology University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. J.","family":"Niemi","sequence":"additional","affiliation":[{"name":"Department of Bacteriology and Immunology University of Helsinki Helsinki Finland"},{"name":"Research Programs Unit Immunobiology University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6045-108X","authenticated-orcid":false,"given":"E.","family":"Kek\u00e4l\u00e4inen","sequence":"additional","affiliation":[{"name":"Department of Bacteriology and Immunology University of Helsinki Helsinki Finland"},{"name":"Research Programs Unit Immunobiology University of Helsinki Helsinki Finland"},{"name":"HUSLAB Division of Clinical Microbiology Helsinki University Hospital, HUS Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Laine","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Paulin","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Auvinen","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. 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