{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:56:41Z","timestamp":1789707401079,"version":"4.0.1"},"reference-count":51,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,12,23]],"date-time":"2015-12-23T00:00:00Z","timestamp":1450828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000341","name":"Arthritis Research UK","doi-asserted-by":"crossref","award":["19307"],"award-info":[{"award-number":["19307"]}],"id":[{"id":"10.13039\/501100000341","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Innovative Medicines Initiative (BTCure)","award":["115142-2"],"award-info":[{"award-number":["115142-2"]}]},{"name":"Department of Health (NIHR Biomedical Research Centre award to Guy's and St. Thomas\u2019 NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Conflicting evidence exists regarding the suppressive capacity of Treg cells in the peripheral blood (PB) of patients with rheumatoid arthritis (RA). The aim of this study was to determine whether Treg cells are intrinsically defective in RA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using a range of assays on PB samples from patients with chronic RA and healthy controls, CD3+CD4+CD25+CD127<jats:sup>low<\/jats:sup> Treg cells from the CD45RO+ or CD45RA+ T cell compartments were analyzed for phenotype, cytokine expression (ex vivo and after in vitro stimulation), suppression of Teff cell proliferation and cytokine production, suppression of monocyte\u2010derived cytokine\/chemokine production, and gene expression profiles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>No differences between RA patients and healthy controls were observed with regard to the frequency of Treg cells, ex vivo phenotype (CD4, CD25, CD127, CD39, or CD161), or proinflammatory cytokine profile (interleukin\u201017 [IL\u201017], interferon\u2010\u03b3 [IFN\u03b3], or tumor necrosis factor [TNF]). FoxP3 expression was slightly increased in Treg cells from RA patients. The ability of Treg cells to suppress the proliferation of T cells or the production of cytokines (IFN\u03b3 or TNF) upon coculture with autologous CD45RO+ Teff cells and monocytes was not significantly different between RA patients and healthy controls. In PB samples from some RA patients, CD45RO+ Treg cells showed an impaired ability to suppress the production of certain cytokines\/chemokines (IL\u20101\u03b2, IL\u20101 receptor antagonist, IL\u20107, CCL3, or CCL4) by autologous lipopolysaccharide\u2010activated monocytes. However, this was not observed in all patients, and other cytokines\/chemokines (TNF, IL\u20106, IL\u20108, IL\u201012, IL\u201015, or CCL5) were generally suppressed. Finally, gene expression profiling of CD45RA+ or CD45RO+ Treg cells from the PB revealed no statistically significant differences between RA patients and healthy controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings indicate that there is no global defect in either CD45RO+ or CD45RA+ Treg cells in the PB of patients with chronic RA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39408","type":"journal-article","created":{"date-parts":[[2015,8,28]],"date-time":"2015-08-28T10:50:23Z","timestamp":1440759023000},"page":"103-116","source":"Crossref","is-referenced-by-count":54,"title":["Phenotypic, Functional, and Gene Expression Profiling of Peripheral CD45RA+ and CD45RO+ CD4+CD25+CD127<sup>low<\/sup> Treg Cells in Patients With Chronic Rheumatoid Arthritis"],"prefix":"10.1002","volume":"68","author":[{"given":"Gina J.","family":"Walter","sequence":"first","affiliation":[{"name":"King's College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veerle","family":"Fleskens","sequence":"additional","affiliation":[{"name":"King's College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus S.","family":"Frederiksen","sequence":"additional","affiliation":[{"name":"Novo Nordisk M\u00e5l\u00f8v Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megha","family":"Rajasekhar","sequence":"additional","affiliation":[{"name":"King's College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bina","family":"Menon","sequence":"additional","affiliation":[{"name":"Guy's and St. Thomas\u2019 NHS Foundation Trust London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens G.","family":"Gerwien","sequence":"additional","affiliation":[{"name":"Novo Nordisk M\u00e5l\u00f8v Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayley G.","family":"Evans","sequence":"additional","affiliation":[{"name":"King's College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonie S.","family":"Taams","sequence":"additional","affiliation":[{"name":"King's College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,12,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/immu.200390024"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20499"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.2005.01656.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2005.02754.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kel089"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/03009740701482800"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900007"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.37832"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.11063"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar1484"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21195"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22272"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20040165"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3085"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-11-4567"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1186068"},{"key":"e_1_2_7_18_1","first-page":"2344","article-title":"Treg cell function in rheumatoid arthritis is compromised by CTLA\u20104 promoter methylation resulting in a failure to activate the indoleamine 2,3\u2010dioxygenase pathway. 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