{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T02:44:39Z","timestamp":1761101079927},"reference-count":62,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2011,11,21]],"date-time":"2011-11-21T00:00:00Z","timestamp":1321833600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Transfusion"],"published-print":{"date-parts":[[2012,6]]},"abstract":"<jats:p><jats:bold>BACKGROUND:<\/jats:bold> Human cord blood (CB) is a superior source of regulatory T cells (Tregs) compared with peripheral blood. Initial studies have shown that CB\u2010derived Tregs can be effectively expanded ex vivo. However, in vitro suppressor activity of expanded CB\u2010Tregs and their efficacy in the prevention of acute graft\u2010versus\u2010host disease (aGVHD) in vivo are poorly understood.<\/jats:p><jats:p><jats:bold>STUDY DESIGN AND METHODS:<\/jats:bold> In vitro, human CB CD4+CD25+ T cells expanded with anti\u2010CD3\/CD28 beads plus interleukin (IL)\u20102 and the phenotypes, expression of cytokines, and suppression of expanded cells were analyzed after two cycles of stimulation. In vivo, the addition of human CB\u2010Tregs was transferred in the major histocompatibility complex\u2013mismatched aGVHD mouse model. Survival, body weight, GVHD scoring, histopathologic specimens, serum cytokines, and Th subsets were analyzed in CB\u2010Treg\u2013treated mice and untreated controls.<\/jats:p><jats:p><jats:bold>RESULTS:<\/jats:bold> After being expanded ex vivo, human CB\u2010derived Tregs with potent suppressor function could meet clinical demands. Up to 85% of mice with CB\u2010Tregs treatment survived beyond Day 63 after bone marrow transplantation; however, all aGVHD mice died within 18 days. In the serum of the CB\u2010Treg\u2013treated mice, the production of transforming growth factor\u2010\u03b2 increased continuously, as opposed to IL\u201017, which decreased quickly. Consistent with the changes of cytokines, the percentage of mouse CD4+ forkhead box protein 3+ Tregs increased while that of Th17 cells decreased.<\/jats:p><jats:p><jats:bold>CONCLUSION:<\/jats:bold> Ex vivo expanded human CB\u2010Tregs significantly prevented allogeneic aGVHD in vivo by modulating various cytokine secretion and polarizing the Treg\/Th17 balance toward Treg, which suggests the potential use of expanded CB\u2010Tregs as a therapeutic approach for GVHD.<\/jats:p>","DOI":"10.1111\/j.1537-2995.2011.03448.x","type":"journal-article","created":{"date-parts":[[2011,11,21]],"date-time":"2011-11-21T06:58:54Z","timestamp":1321858734000},"page":"1333-1347","source":"Crossref","is-referenced-by-count":14,"title":["Amelioration of acute graft\u2010versus\u2010host disease by adoptive transfer of ex vivo expanded human cord blood CD4+CD25+ forkhead box protein 3+ regulatory T cells is associated with the polarization of Treg\/Th17 balance in a mouse 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