{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T21:07:32Z","timestamp":1791148052820,"version":"4.1.0"},"reference-count":49,"publisher":"American Society of Hematology","issue":"23","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,6,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>FoxP3+ regulatory T cells (Tregs) suppress GVHD while preserving graft-versus-tumor effects, making them an attractive target for GVHD therapy. The donor-derived Treg pool can potentially be derived from the expansion of preexisting natural Tregs (nTregs) or from de novo generation of inducible Tregs (iTregs) from donor Tconvs in the transplantation recipient. Using an MHC-mismatched model of acute GVHD, in the present study we found that the Treg pool was comprised equally of donor-derived nTregs and iTregs. Experiments using various combinations of T cells from wild-type and FoxP3-deficient mice suggested that both preexisting donor nTregs and the generation of iTregs in the recipient mice contribute to protection against GVHD. Surprisingly, CD8+FoxP3+ T cells represented approximately 70% of the iTreg pool. These CD8+FoxP3+ T cells shared phenotypic markers with their CD4+ counterparts and displayed suppressive activity, suggesting that they were bona fide iTregs. Both CD4+ and CD8+ Tregs appeared to be protective against GVHD-induced lethality and required IL-2 and TGF\u03b2 receptor expression for their generation. These data illustrate the complex makeup of the donor-derived FoxP3+ Treg pool in allogeneic recipients and their potential role in protection against GVHD.<\/jats:p>","DOI":"10.1182\/blood-2011-07-367987","type":"journal-article","created":{"date-parts":[[2012,4,11]],"date-time":"2012-04-11T03:24:27Z","timestamp":1334114667000},"page":"5575-5583","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":44,"title":["Cell-autonomous role of TGF\u03b2 and IL-2 receptors in CD4+ and CD8+ inducible regulatory T-cell generation during GVHD"],"prefix":"10.1182","volume":"119","author":[{"given":"Norifumi","family":"Sawamukai","sequence":"first","affiliation":[{"name":"Transfusion Medicine and Therapeutic Pathology Division, Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; and"},{"name":"First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Satake","sequence":"additional","affiliation":[{"name":"Transfusion Medicine and Therapeutic Pathology Division, Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda M.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Transfusion Medicine and Therapeutic Pathology Division, Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian T.","family":"Lamborn","sequence":"additional","affiliation":[{"name":"Transfusion Medicine and Therapeutic Pathology Division, Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priti","family":"Ojha","sequence":"additional","affiliation":[{"name":"Transfusion Medicine and Therapeutic Pathology Division, Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiya","family":"Tanaka","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taku","family":"Kambayashi","sequence":"additional","affiliation":[{"name":"Transfusion Medicine and Therapeutic Pathology Division, Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"5","key":"2019111811520583300_B1","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.cell.2008.05.009","article-title":"Regulatory T cells and immune tolerance.","volume":"133","author":"Sakaguchi","year":"2008","journal-title":"Cell"},{"issue":"5","key":"2019111811520583300_B2","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.immuni.2009.04.009","article-title":"Control of regulatory T cell lineage commitment and maintenance.","volume":"30","author":"Josefowicz","year":"2009","journal-title":"Immunity"},{"issue":"2","key":"2019111811520583300_B3","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.coi.2007.02.005","article-title":"Thymic development and peripheral homeostasis of regulatory T cells.","volume":"19","author":"Liston","year":"2007","journal-title":"Curr Opin Immunol"},{"issue":"4","key":"2019111811520583300_B4","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/ni904","article-title":"Foxp3 programs the development and function of CD4+CD25+ regulatory T cells.","volume":"4","author":"Fontenot","year":"2003","journal-title":"Nat Immunol"},{"issue":"3","key":"2019111811520583300_B5","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.4049\/jimmunol.155.3.1151","article-title":"Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). 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