{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:51:38Z","timestamp":1791229898222,"version":"4.1.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2006,4,1]],"date-time":"2006-04-01T00:00:00Z","timestamp":1143849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Anomalies of naturally occurring CD4+ regulatory T cells (Treg) cause severe autoimmune\/inflammatory diseases in humans and rodents. The transcription factor Foxp3 is currently the most specific marker for natural CD4+ Treg, but it would be useful if other Treg markers, particularly cell surface molecules, could be elucidated. We demonstrate in this study that the vast majority of Foxp3-expressing CD4+ T cells (whether CD25+ or CD25\u2212) show constitutive high-level expression of glucocorticoid-induced TNFR family-related gene\/protein (GITR). Transfer of T cell or thymocyte suspensions depleted of GITRhigh cells produces in BALB\/c nude mice a wider spectrum and more severe forms of autoimmune diseases than does transfer of similar cell suspensions depleted of CD25+CD4+ T cells only. Notably, mice that receive cells depleted of GITRhigh populations develop severe multiorgan inflammation that includes fatal autoimmune myocarditis resembling giant cell myocarditis in humans, accompanying high-titer anti-myosin autoantibodies. Similar transfer of GITRhigh-depleted cells from prediabetic NOD mice to NOD-SCID mice accelerates the development of diabetes and induces skeletal muscle myositis and other autoimmune\/inflammatory diseases. We conclude that GITRhigh, Foxp3-expressing natural Treg, containing both CD25+ and CD25\u2212 cell populations, contribute to preventing a variety of autoimmune\/inflammatory diseases, and depletion of these cells allows the activation of even weak or rare autoreactive T cells yielding widespread severe autoimmune disease. Diseases induced in this way include many which have been suspected of an autoimmune etiology in humans without much evidence. GITRhigh, Foxp3-expressing natural Treg represent a potential target for the treatment and prevention of these diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.176.8.4748","type":"journal-article","created":{"date-parts":[[2014,4,23]],"date-time":"2014-04-23T20:59:46Z","timestamp":1398286786000},"page":"4748-4756","source":"Crossref","is-referenced-by-count":142,"title":["Control of Autoimmune Myocarditis and Multiorgan Inflammation by Glucocorticoid-Induced TNF Receptor Family-Related Proteinhigh, Foxp3-Expressing CD25+ and CD25\u2212 Regulatory T Cells"],"prefix":"10.1093","volume":"176","author":[{"given":"Masahiro","family":"Ono","sequence":"first","affiliation":[{"name":"Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University , Kyoto ,","place":["Japan"]},{"name":"Department of Dermatology, Graduate School of Medicine, Kyoto University , Kyoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Tokyo Metropolitan Institute for Gerontology , Itabashi-ku, Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Miyachi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, Kyoto University , Kyoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimon","family":"Sakaguchi","sequence":"additional","affiliation":[{"name":"Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University , Kyoto ,","place":["Japan"]},{"name":"Core Research for Evolutional Science and Technology, Japan Science and Technology Agency , Kawaguchi ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2006,4,15]]},"reference":[{"key":"2026020211344567800_R1","first-page":"816","volume-title":"Nat. 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