{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T03:22:45Z","timestamp":1791170565008,"version":"4.1.0"},"reference-count":87,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2003,10,1]],"date-time":"2003-10-01T00:00:00Z","timestamp":1064966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI 41768"],"award-info":[{"award-number":["AI 41768"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Nora Eccles Treadwell Foundation"},{"DOI":"10.13039\/100000980","name":"Arthritis Foundation, Southern California Chapter","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000980","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Recently, considerable attention has been focused on thymus-derived CD4+ regulatory T cells that constitutively express CD25 and have a contact-dependent, cytokine-independent mechanism in vitro. However, peripheral CD4+ and CD8+ T cells can also be induced to become regulatory T cells. Here we review our studies using the combination of IL-2 and transforming growth factor \u03b2 (TGF-\u03b2) to generate regulatory T cell subsets ex vivo, and the work of others using IL-10 to induce suppressive activity. Under certain conditions, the autocrine effects of TGF-\u03b2 and IL-10 induce peripheral T cells to produce immunosuppressive levels of each of these cytokines. This effect of TGF-\u03b2 is IL-2 dependent. Under other conditions IL-2 and TGF-\u03b2 can induce CD4+ cells to develop potent contact-dependent, cytokine-independent regulatory activity. At present, there is considerable confusion concerning the mechanism of action of CD4+ CD25+ cells because cytokine-producing regulatory T cells generated in the periphery can express CD25 and other markers displayed by naturally occurring, thymus-derived regulatory T cells. We, therefore, propose a nomenclature that identifies thymus-derived and peripheral regulatory cells, and that also differentiates T regulatory cells from T helper cells. Because T regulatory cells broadly control T helper cell reactivity, the mechanisms that control regulatory cell function are also reviewed. Finally, the potential use of regulatory T cells generated ex vivo as an adoptive immunotherapy for certain autoimmune diseases, to prevent organ graft rejection, or to prevent pathologic host responses to infectious agents is discussed.<\/jats:p>","DOI":"10.1189\/jlb.0503228","type":"journal-article","created":{"date-parts":[[2003,9,30]],"date-time":"2003-09-30T23:19:04Z","timestamp":1064963944000},"page":"471-478","source":"Crossref","is-referenced-by-count":143,"title":["The role of the combination of IL-2 and TGF-\u03b2 or IL-10 in the generation and function of CD4+ CD25+ and CD8+regulatory T cell subsets"],"prefix":"10.1093","volume":"74","author":[{"given":"David A","family":"Horwitz","sequence":"first","affiliation":[{"name":"Division of Rheumatology and Immunology, Department of Medicine, Keck School of Medicine of the University of Southern California , Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song Guo","family":"Zheng","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Immunology, Department of Medicine, Keck School of Medicine of the University of Southern California , Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Dixon","family":"Gray","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Immunology, Department of Medicine, Keck School of Medicine of the University of Southern California , Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2003,10,1]]},"reference":[{"key":"2023033100391883300_jlb0471-cit-B1","first-page":"170","article-title":"A disquisition on suppressor T cells","volume":"26","author":"Gershon","year":"1975","journal-title":"Transplant. 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