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Using the glucose\u20106\u2010phosphate isomerase (G6PI)\u2010induced arthritis model in mice, we aimed to determine the therapeutic efficacy of increasing Treg cell number and function during chronic destructive arthritis. Chronic destructive arthritis was induced by transient depletion of Treg cells prior to immunization with G6PI. At different time points after disease induction, mice were treated with a CD28 superagonistic antibody (CD28SA). CD28SA treatment during the induction phase of arthritis ameliorated the acute signs of arthritis and completely prevented the development of chronic destructive arthritis. CD28SA treatment of mice with fully developed arthritis induced a significant reduction in clinical and histological signs of arthritis. When given during the chronic destructive phase of arthritis, 56 days after disease induction, CD28SA treatment resulted in a modest reduction of clinical signs of arthritis and a reduction in histopathological signs of joint inflammation. Our data show that increasing the number and activation of Treg cells by a CD28SA is therapeutically effective in experimental arthritis.<\/jats:p>","DOI":"10.1002\/eji.201546104","type":"journal-article","created":{"date-parts":[[2015,12,29]],"date-time":"2015-12-29T08:46:41Z","timestamp":1451378801000},"page":"1193-1202","source":"Crossref","is-referenced-by-count":11,"title":["In vivo activation of Treg cells with a CD28 superagonist prevents and ameliorates chronic destructive arthritis in mice"],"prefix":"10.1002","volume":"46","author":[{"given":"Stephanie J.","family":"Win","sequence":"first","affiliation":[{"name":"Institute of Immunology Universit\u00e4tsklinikum Jena  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja A.","family":"K\u00fchl","sequence":"additional","affiliation":[{"name":"Department of Medicine 1\u2010Gastroenterology Infectious Diseases and Rheumatology and Research Centre ImmunoSciences Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Sparwasser","sequence":"additional","affiliation":[{"name":"Institute for Infection Immunology Centre for Experimental and Clinical Infection Research TWINCORE  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"H\u00fcnig","sequence":"additional","affiliation":[{"name":"Institute of Virology and Immunobiology University of W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kamradt","sequence":"additional","affiliation":[{"name":"Institute of Immunology Universit\u00e4tsklinikum Jena  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,1,20]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1004965"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00178"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.03.002"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.11063"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar1484"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22272"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-12-128488"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21195"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2007.086066"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1103598"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/immu.200390024"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20499"},{"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":"10.1111\/j.1365-2249.2005.02754.x"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22414"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0806855105"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2012.149"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-12-328187"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2014.105"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200323570"},{"key":"e_1_2_7_22_1","first-page":"110","article-title":"Effective treatment of adjuvant arthritis with a stimulatory CD28\u2010specific monoclonal antibody","volume":"33","author":"Rodriguez\u2010Palmero M.","year":"2006","journal-title":"J. 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