{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T23:10:42Z","timestamp":1787613042016,"version":"build-2736575974"},"reference-count":70,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2015,6,1]],"date-time":"2015-06-01T00:00:00Z","timestamp":1433116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Expansion of Ag-specific naturally occurring regulatory T cells (nTregs) is required to obtain sufficient numbers of cells for cellular immunotherapy. In this study, different allogeneic stimuli were studied for their capacity to generate functional alloantigen-specific nTregs. A highly enriched nTreg fraction (CD4+CD25brightCD127\u2212 T cells) was alloantigen-specific expanded using HLA-mismatched immature, mature monocyte-derived dendritic cells (moDCs), or PBMCs. The allogeneic mature moDC-expanded nTregs were fully characterized by analysis of the demethylation status within the Treg-specific demethylation region of the FOXP3 gene and the expression of both protein and mRNA of FOXP3, HELIOS, CTLA4, and cytokines. In addition, the Ag-specific suppressive capacity of these expanded nTregs was tested. Allogeneic mature moDCs and skin-derived DCs were superior in inducing nTreg expansion compared with immature moDCs or PBMCs in an HLA-DR\u2013 and CD80\/CD86-dependent way. Remarkably, the presence of exogenous IL-15 without IL-2 could facilitate optimal mature moDC-induced nTreg expansion. Allogeneic mature moDC-expanded nTregs were at low ratios (&amp;lt;1:320), potent suppressors of alloantigen-induced proliferation without significant suppression of completely HLA-mismatched, Ag-induced proliferation. Mature moDC-expanded nTregs were highly demethylated at the Treg-specific demethylation region within the FOXP3 gene and highly expressed of FOXP3, HELIOS, and CTLA4. A minority of the expanded nTregs produced IL-10, IL-2, IFN-\u03b3, and TNF-\u03b1, but few IL-17\u2013producing nTregs were found. Next-generation sequencing of mRNA of moDC-expanded nTregs revealed a strong induction of Treg-associated mRNAs. Human allogeneic mature moDCs are highly efficient stimulator cells, in the presence of exogenous IL-15, for expansion of stable alloantigen-specific nTregs with superior suppressive function.<\/jats:p>","DOI":"10.4049\/jimmunol.1402827","type":"journal-article","created":{"date-parts":[[2015,4,28]],"date-time":"2015-04-28T01:41:13Z","timestamp":1430185273000},"page":"5282-5293","source":"Crossref","is-referenced-by-count":15,"title":["Allogeneic Mature Human Dendritic Cells Generate Superior Alloreactive Regulatory T Cells in the Presence of IL-15"],"prefix":"10.1093","volume":"194","author":[{"given":"Nicolle H R","family":"Litjens","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Nephrology and Transplantation, Erasmus Medical Center , 3000 CA Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Boer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Nephrology and Transplantation, Erasmus Medical Center , 3000 CA Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joke M","family":"Zuijderwijk","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Nephrology and Transplantation, Erasmus Medical Center , 3000 CA Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariska","family":"Klepper","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Nephrology and Transplantation, Erasmus Medical Center , 3000 CA Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemiek M A","family":"Peeters","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Nephrology and Transplantation, Erasmus Medical Center , 3000 CA Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Errol P","family":"Prens","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Erasmus Medical Center , 3000 CA Rotterdam ,","place":["the Netherlands"]},{"name":"Department of Rheumatology, Erasmus Medical Center , 3000 CA Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenda","family":"Verschoor","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Nephrology and Transplantation, Erasmus Medical Center , 3000 CA Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rens","family":"Kraaijeveld","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Nephrology and Transplantation, Erasmus Medical Center , 3000 CA Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeliha","family":"Ozgur","sequence":"additional","affiliation":[{"name":"Erasmus Medical Center, Erasmus Center for Biomics , 3000 CA Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam C","family":"van den Hout-van Vroonhoven","sequence":"additional","affiliation":[{"name":"Erasmus Medical Center, Erasmus Center for Biomics , 3000 CA Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfred F J","family":"van IJcken","sequence":"additional","affiliation":[{"name":"Erasmus Medical Center, Erasmus Center for Biomics , 3000 CA Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla C","family":"Baan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Nephrology and Transplantation, Erasmus Medical Center , 3000 CA Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiel G H","family":"Betjes","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Nephrology and Transplantation, Erasmus Medical Center , 3000 CA Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,6,1]]},"reference":[{"key":"2025030706374282600_r1","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.autrev.2005.04.010","article-title":"Thymic regulatory T cells","volume":"4","author":"Maggi","year":"2005","journal-title":"Autoimmun. 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