{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:11:22Z","timestamp":1792113082406,"version":"4.4.0"},"reference-count":14,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,1,27]],"date-time":"2014-01-27T00:00:00Z","timestamp":1390780800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Autologous stem cell transplantation (ASCT) induces long\u2010term drug\u2010free disease remission in patients with juvenile idiopathic arthritis. This study was undertaken to further unravel the immunologic mechanisms underlying ASCT by using a mouse model of proteoglycan\u2010induced arthritis (PGIA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>For initiation of PGIA, BALB\/c mice received 2 intraperitoneal injections of human PG in a synthetic adjuvant on days 0 and 21. Five weeks after the first immunization, the mice were exposed to total body irradiation (7.5 Gy) and received (un)manipulated bone marrow (BM) grafts from mice with PGIA. Clinical scores, T cell reconstitution, (antigen\u2010specific) T cell cytokine production, and intracellular cytokine expression were determined following autologous BM transplantation (ABMT).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ABMT resulted in amelioration and stabilization of arthritis scores. BM grafts containing T cells and T cell\u2013depleted grafts provided the same clinical benefit, with similar reductions in PG\u2010induced T cell proliferation and the number of PG\u2010specific autoantibodies. In vivo reexposure to PG did not exacerbate disease. Following ABMT, basal levels of disease\u2010associated proinflammatory cytokines (interferon\u2010\u03b3 [IFN\u03b3], interleukin\u201017 [IL\u201017], and tumor necrosis factor \u03b1 [TNF\u03b1]) were reduced. In addition, restimulation of T cells with PG induced a strong reduction in disease\u2010associated proinflammatory cytokine production. Finally, although the remaining host T cells displayed a proinflammatory phenotype following ABMT, IFN\u03b3, IL\u201017, and TNF\u03b1 production by the newly reconstituted donor\u2010derived T cells was significantly lower.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Taken together, our data suggest that ABMT restores immune tolerance by renewal and modulation of the Teff cell compartment, leading to a strong reduction in proinflammatory (self antigen\u2013specific) T cell cytokine production.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38261","type":"journal-article","created":{"date-parts":[[2013,10,31]],"date-time":"2013-10-31T19:08:25Z","timestamp":1383246505000},"page":"350-356","source":"Crossref","is-referenced-by-count":17,"title":["Brief Report: Autologous Stem Cell Transplantation Restores Immune Tolerance in Experimental Arthritis by Renewal and Modulation of the Teff Cell Compartment"],"prefix":"10.1002","volume":"66","author":[{"given":"Eveline M.","family":"Delemarre","sequence":"first","affiliation":[{"name":"University Medical Center Utrecht and Wilhelmina Children's Hospital Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah T. A.","family":"Roord","sequence":"additional","affiliation":[{"name":"University Medical Center Utrecht and Wilhelmina Children's Hospital Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theo","family":"van den Broek","sequence":"additional","affiliation":[{"name":"University Medical Center Utrecht and Wilhelmina Children's Hospital Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelien","family":"Zonneveld\u2010Huijssoon","sequence":"additional","affiliation":[{"name":"University Medical Center Utrecht and Wilhelmina Children's Hospital Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilco","family":"de Jager","sequence":"additional","affiliation":[{"name":"University Medical Center Utrecht and Wilhelmina Children's Hospital Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henk","family":"Rozemuller","sequence":"additional","affiliation":[{"name":"University Medical Center Utrecht and Wilhelmina Children's Hospital Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton C.","family":"Martens","sequence":"additional","affiliation":[{"name":"University Medical Center Utrecht and Wilhelmina Children's Hospital Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Femke","family":"Broere","sequence":"additional","affiliation":[{"name":"University of Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nico M.","family":"Wulffraat","sequence":"additional","affiliation":[{"name":"University Medical Center Utrecht and Wilhelmina Children's Hospital Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tibor T.","family":"Glant","sequence":"additional","affiliation":[{"name":"Rush University Medical Center Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berent J.","family":"Prakken","sequence":"additional","affiliation":[{"name":"University Medical Center Utrecht and Wilhelmina Children's Hospital Utrecht The Netherlands"},{"name":"the Eureka Institute for Translational Medicine Siracusa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Femke","family":"van Wijk","sequence":"additional","affiliation":[{"name":"University Medical Center Utrecht and Wilhelmina Children's Hospital Utrecht The Netherlands"},{"name":"the Eureka Institute for Translational Medicine Siracusa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,1,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0b013e32835264f4"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)05399-9"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22656"},{"key":"e_1_2_7_5_1","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1182\/blood-2005-07-2800","article-title":"Autologous stem cell transplantation for autoimmunity induces immunologic self\u2010tolerance by reprogramming autoreactive T cells and restoring the CD4+CD25+ immune regulatory network","volume":"107","author":"Kleer I","year":"2006","journal-title":"Blood"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2004.033332"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20041679"},{"key":"e_1_2_7_8_1","first-page":"313","article-title":"Proteoglycan aggrecan\u2010induced arthritis: a murine autoimmune model of rheumatoid arthritis","volume":"102","author":"Glant TT","year":"2004","journal-title":"Methods Mol Med"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevImmunol.v23.i3.20"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-12-128488"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V88.7.2775.bloodjournal8872775"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2011.185"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-02-336156"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902907"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.1.329"}],"container-title":["Arthritis &amp; 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