{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:18:10Z","timestamp":1791289090978,"version":"4.3.0"},"reference-count":188,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2012,1,5]],"date-time":"2012-01-05T00:00:00Z","timestamp":1325721600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Toxicol Pathol"],"published-print":{"date-parts":[[2012,2]]},"abstract":"<jats:p>\n                    Regulatory T-cells (T\n                    <jats:sub>REG<\/jats:sub>\n                    ) are diverse populations of lymphocytes that regulate the adaptive immune response in higher vertebrates. T\n                    <jats:sub>REG<\/jats:sub>\n                    delete autoreactive T-cells, induce tolerance, and dampen inflammation. T\n                    <jats:sub>REG<\/jats:sub>\n                    cell deficiency in humans (i.e., IPEX [Immunodysregulation, Polyendocrinopathy and Enteropathy, X-linked syndrome]) and animal models (e.g., \u201cScurfy\u201d mouse) is associated with multisystemic autoimmune disease. T\n                    <jats:sub>REG<\/jats:sub>\n                    in humans and laboratory animal species are similar in type and regulatory function. A molecular marker of and the cell lineage specification factor for T\n                    <jats:sub>REG<\/jats:sub>\n                    is FOXP3, a forkhead box transcription factor. CD4\n                    <jats:sup>+<\/jats:sup>\n                    T\n                    <jats:sub>REG<\/jats:sub>\n                    are either natural (nT\n                    <jats:sub>REG<\/jats:sub>\n                    ), which are thymus-derived CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD25\n                    <jats:sup>+<\/jats:sup>\n                    FOXP3\n                    <jats:sup>+<\/jats:sup>\n                    T-cells, or inducible (i.e., Tr1 cells that secrete IL-10, Th3 cells that secrete TGF-\u03b2 and IL-10, and Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    Treg). The proinflammatory Th17 subset has been a major focus of research. T\n                    <jats:sub>H<\/jats:sub>\n                    17 CD4\n                    <jats:sup>+<\/jats:sup>\n                    effector T-cells secrete IL-17, IL-21, and IL-22 in autoimmune and inflammatory disease, and are dynamically balanced with T\n                    <jats:sub>REG<\/jats:sub>\n                    cell development. Other lymphocyte subsets with regulatory function include: inducible CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\n                    <jats:sub>REG<\/jats:sub>\n                    , CD3\n                    <jats:sup>+<\/jats:sup>\n                    CD4\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD8\n                    <jats:sup>\u2212<\/jats:sup>\n                    T\n                    <jats:sub>REG<\/jats:sub>\n                    (double-negative), CD4\n                    <jats:sup>+<\/jats:sup>\n                    V\u03b114\n                    <jats:sup>+<\/jats:sup>\n                    (NKT\n                    <jats:sub>REG<\/jats:sub>\n                    ), and \u03b3\u03b4 T-cells. T\n                    <jats:sub>REG<\/jats:sub>\n                    have four regulatory modes of action: secretion of inhibitory cytokines (e.g., IL-10 and TGF-\u03b2), granzyme-perforin-induced apoptosis of effector lymphocytes, depriving effector T-cells of cytokines leading to apoptosis, or inhibition of dendritic cell function. The role of T\n                    <jats:sub>REG<\/jats:sub>\n                    in mucosal sites, inflammation\/infection, pregnancy, and cancer as well as a review of T\n                    <jats:sub>REG<\/jats:sub>\n                    as a modulatory target in drug development will be covered.\n                  <\/jats:p>","DOI":"10.1177\/0192623311430693","type":"journal-article","created":{"date-parts":[[2012,1,6]],"date-time":"2012-01-06T06:44:12Z","timestamp":1325832252000},"page":"186-204","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":198,"title":["Regulatory T-Cells: Diverse Phenotypes Integral to Immune Homeostasis and Suppression"],"prefix":"10.1177","volume":"40","author":[{"given":"Richard A.","family":"Peterson","sequence":"first","affiliation":[{"name":"GlaxoSmithKline, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2012,1,5]]},"reference":[{"key":"bibr1-0192623311430693","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.5.2454-2459.2004"},{"key":"bibr2-0192623311430693","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.20894"},{"key":"bibr3-0192623311430693","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.02.012"},{"key":"bibr4-0192623311430693","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2009.07.012"},{"key":"bibr5-0192623311430693","doi-asserted-by":"publisher","DOI":"10.1038\/ni1037"},{"key":"bibr6-0192623311430693","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.6.3143"},{"key":"bibr7-0192623311430693","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-8411(03)00045-3"},{"key":"bibr8-0192623311430693","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2008.03.001"},{"key":"bibr9-0192623311430693","doi-asserted-by":"publisher","DOI":"10.1081\/IMM-120004800"},{"key":"bibr10-0192623311430693","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2006.03.023"},{"key":"bibr11-0192623311430693","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.12.8338"},{"key":"bibr12-0192623311430693","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700004"},{"key":"bibr13-0192623311430693","doi-asserted-by":"publisher","DOI":"10.1038\/nature01152"},{"key":"bibr14-0192623311430693","doi-asserted-by":"publisher","DOI":"10.1038\/ni1181"},{"key":"bibr15-0192623311430693","doi-asserted-by":"publisher","DOI":"10.1038\/nature04753"},{"key":"bibr16-0192623311430693","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.1.246"},{"key":"bibr17-0192623311430693","doi-asserted-by":"publisher","DOI":"10.1016\/j.cvsm.2007.12.006"},{"key":"bibr18-0192623311430693","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-10-3014"},{"key":"bibr19-0192623311430693","doi-asserted-by":"publisher","DOI":"10.1016\/j.trre.2006.06.004"},{"key":"bibr20-0192623311430693","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2005.09.002"},{"key":"bibr21-0192623311430693","doi-asserted-by":"publisher","DOI":"10.1159\/000235851"},{"key":"bibr22-0192623311430693","doi-asserted-by":"crossref","first-page":"3681","DOI":"10.4049\/jimmunol.160.8.3681","volume":"160","author":"Brossay L.","year":"1998","journal-title":"J Immunol"},{"key":"bibr23-0192623311430693","doi-asserted-by":"publisher","DOI":"10.1038\/83784"},{"key":"bibr24-0192623311430693","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20454"},{"key":"bibr25-0192623311430693","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021633"},{"key":"bibr26-0192623311430693","doi-asserted-by":"publisher","DOI":"10.1038\/ni760"},{"key":"bibr27-0192623311430693","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.4.1846"},{"key":"bibr28-0192623311430693","doi-asserted-by":"publisher","DOI":"10.2174\/092986707781696591"},{"key":"bibr29-0192623311430693","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.5.3409"},{"key":"bibr30-0192623311430693","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-122-31353"},{"key":"bibr31-0192623311430693","doi-asserted-by":"crossref","first-page":"2546","DOI":"10.4049\/jimmunol.162.5.2546","volume":"162","author":"Clark L. 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