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We found that a single injection of a small number of expanded but not fresh HY-specific Tregs protected syngeneic male skin grafts from rejection by immune-competent recipients. The expanded Tregs were predominantly located in the grafts and graft-draining lymph nodes. In vitro expanded Tregs displayed a phenotype of CD25highCD4lowFoxp3+CTLA4+, and also up-regulated IL10 and TGF\u03b2 while down-regulating IFN-\u03b3, GM-CSF, IL5, and TNF-\u03b1 production. Furthermore, expanded Tregs appeared to express a reduced level of Foxp3, which could be prevented by adding TGF\u03b2 to the culture, and they also tended to lose Foxp3 following the repeated stimulation. Finally, a proportion of expanded HY-specific Tregs secreted IL2 in response to their cognate peptide, and this finding could be confirmed using Tregs from Foxp3GFP reporter mice. We not only demonstrated that expanded Tregs are superior to fresh Tregs in suppressing T cell responses against alloantigens, but also revealed some novel immunobiological properties of expended Tregs which are very instructive for modifying current Treg expansion procedures.<\/jats:p>","DOI":"10.4049\/jimmunol.180.2.858","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T23:09:13Z","timestamp":1397862553000},"page":"858-869","source":"Crossref","is-referenced-by-count":53,"title":["In Vitro Expansion Improves In Vivo Regulation by CD4+CD25+ Regulatory T Cells"],"prefix":"10.1093","volume":"180","author":[{"given":"Jian-Guo","family":"Chai","sequence":"first","affiliation":[{"name":"Cancer Immunotherapy Group , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Coe","sequence":"additional","affiliation":[{"name":"Cancer Immunotherapy Group , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daxin","family":"Chen","sequence":"additional","affiliation":[{"name":"Transplant Inflammation Group , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Simpson","sequence":"additional","affiliation":[{"name":"Transplantation Biology Group, Department of Immunology, Imperial College London , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Dyson","sequence":"additional","affiliation":[{"name":"Transplantation Biology Group, Department of Immunology, Imperial College London , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Scott","sequence":"additional","affiliation":[{"name":"Transplantation Biology Group, Department of Immunology, Imperial College London , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,1,15]]},"reference":[{"key":"2025032610021473100_R1","first-page":"8","volume-title":"Immunol. 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