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The objective of the study was to evaluate the proportion of CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>low\/-<\/jats:sup>GITR<jats:sup>+<\/jats:sup> T lymphocytes within CD4<jats:sup>+<\/jats:sup> T cells and compare their phenotypic and functional profile with that of CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>high<\/jats:sup>GITR<jats:sup>-<\/jats:sup> T lymphocytes in systemic lupus erythematosus (SLE) patients.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>The percentage of CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>low\/-<\/jats:sup>GITR<jats:sup>+<\/jats:sup> cells circulating in the peripheral blood (PB) of 32 patients with SLE and 25 healthy controls was evaluated with flow cytometry. CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>low\/-<\/jats:sup>GITR<jats:sup>+<\/jats:sup> cells were isolated with magnetic separation, and their phenotype was compared with that of CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>high<\/jats:sup>GITR<jats:sup>-<\/jats:sup> cells. Regulatory activity of both cell subsets was tested in autologous and heterologous co-cultures after purification through a negative sorting strategy.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>Results indicated that CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>low\/-<\/jats:sup>GITR<jats:sup>+<\/jats:sup> cells are expanded in the PB of 50% of SLE patients. Expansion was observed only in patients with inactive disease. Phenotypic analysis demonstrated that CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>low\/-<\/jats:sup>GITR<jats:sup>+<\/jats:sup> cells display regulatory T-cell (Treg) markers, including FoxP3, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), transforming growth factor-beta (TGF-\u03b2), and interleukin (IL)-10. In contrast, CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>high<\/jats:sup>GITR<jats:sup>-<\/jats:sup> cells appear to be activated and express low levels of Treg markers. Functional experiments demonstrated that CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>low\/-<\/jats:sup>GITR<jats:sup>+<\/jats:sup> cells exert a higher inhibitory activity against both autologous and heterologous cells as compared with CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>high<\/jats:sup>GITR<jats:sup>-<\/jats:sup> cells. Suppression is independent of cell contact and is mediated by IL-10 and TGF-\u03b2.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>Phenotypic and functional data demonstrate that in SLE patients, CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>low\/-<\/jats:sup>GITR<jats:sup>+<\/jats:sup> cells are fully active Treg cells, possibly representing peripheral Treg (pTreg) that are expanded in patients with inactive disease. These data may suggest a key role of this T-cell subset in the modulation of the abnormal immune response in SLE. Strategies aimed at expanding this Treg subset for therapeutic purpose deserve to be investigated.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/s13075-014-0444-x","type":"journal-article","created":{"date-parts":[[2014,9,25]],"date-time":"2014-09-25T10:54:29Z","timestamp":1411642469000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Expansion of regulatory GITR+CD25low\/-CD4+ T cells in systemic lupus erythematosus patients"],"prefix":"10.1186","volume":"16","author":[{"given":"Giuseppe","family":"Nocentini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Alunno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"Petrillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onelia","family":"Bistoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Bartoloni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Caterbi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Ronchetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graziella","family":"Migliorati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Riccardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Gerli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,9,26]]},"reference":[{"key":"444_CR1","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.jaut.2010.06.018","volume":"35","author":"C Scheinecker","year":"2010","unstructured":"Scheinecker C, Bonelli M, Smolen JS: Pathogenetic aspects of systemic lupus erythematosus with an emphasis on regulatory T cells. 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