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We investigated the <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>regs frequency in patients with multiple myeloma (<jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content>) and in those with monoclonal gammopathy of undetermined significance (<jats:styled-content style=\"fixed-case\">MGUS<\/jats:styled-content>), and found that <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup>FoxP3<jats:sup>+<\/jats:sup> and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup>FoxP3<jats:sup>+<\/jats:sup> Tregs were significantly increased in patients with <jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content> and correlated with the active phase. Both Tregs subsets were expanded in cocultures of <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>3<jats:sup>+<\/jats:sup> lymphocytes and fresh <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>138<jats:sup>+<\/jats:sup> <jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content> plasma cells or <jats:styled-content style=\"fixed-case\">RPMI<\/jats:styled-content>8226 and U266 cell lines and functioned as natural (n) and inducible (i) Tregs insofar as they inhibited the proliferation of stimulated <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>3 lymphocytes via contact\u2010dependent and contact\u2010independent pathways. Induction of Tregs by <jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content> plasma cells required a contact\u2010dependent pathway, implying antigen recognition by T cells. <jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content> plasma cells acted as immature and tolerogenic antigen\u2010presenting cells (<jats:styled-content style=\"fixed-case\">APC<\/jats:styled-content>s), in that they displayed low <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>80\/<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>86 expression associated with a phagocytic activity. By acting as immature <jats:styled-content style=\"fixed-case\">APC<\/jats:styled-content>s, <jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content> plasma cells plausibly expand (n)Tregs and (i)Tregs both through conversion of <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>3<jats:sup>+<\/jats:sup>FoxP3<jats:sup>\u2212<\/jats:sup> into <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>3<jats:sup>+<\/jats:sup>FoxP3<jats:sup>+<\/jats:sup> T cells and proliferation of <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>3<jats:sup>+<\/jats:sup>FoxP3<jats:sup>+<\/jats:sup> T cells, which may suppress the anti\u2010<jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content> immune response.<\/jats:p>","DOI":"10.1111\/ejh.12481","type":"journal-article","created":{"date-parts":[[2014,11,20]],"date-time":"2014-11-20T07:52:20Z","timestamp":1416469940000},"page":"65-74","source":"Crossref","is-referenced-by-count":20,"title":["Myeloma cells act as tolerogenic antigen\u2010presenting cells and induce regulatory <scp>T<\/scp> cells <i>in vitro<\/i>"],"prefix":"10.1111","volume":"95","author":[{"given":"Maria Antonia","family":"Frassanito","sequence":"first","affiliation":[{"name":"General Pathology Unit Department of Biomedical Sciences and Human Oncology University of Bari Medical School Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Ruggieri","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, Histology and Embryology University of Bari Medical School Bari 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