{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:25:18Z","timestamp":1791289518433,"version":"4.3.0"},"reference-count":28,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1999,3,1]]},"abstract":"<jats:p>Previous studies have shown that autoimmune thyroiditis can be induced in normal laboratory rats after thymectomy and split dose \u03b3-irradiation. Development of disease can be prevented by reconstitution of PVG rats shortly after their final irradiation with either peripheral CD4+CD45RC\u2212 T cells or CD4+CD8\u2212 thymocytes from syngeneic donors. Although the activity of both populations is known to depend on the activities of endogenously produced interleukin 4 and transforming growth factor \u03b2, implying a common mechanism, the issue of antigen specificity of the cells involved has not yet been addressed. In this study, we show that the regulatory T cells that prevent autoimmune thyroiditis are generated in vivo only when the relevant autoantigen is also present. Peripheral CD4+ T cells, from rats whose thyroids were ablated in utero by treatment with 131I, were unable to prevent disease development upon adoptive transfer into thymectomized and irradiated recipients. This regulatory deficit is specific for thyroid autoimmunity, since CD4+ T cells from 131I-treated PVG.RT1u rats were as effective as those from normal donors at preventing diabetes in thymectomized and irradiated PVG.RT1u rats. Significantly, in contrast to the peripheral CD4+ T cells, CD4+CD8\u2212 thymocytes from 131I-treated PVG donors were still able to prevent thyroiditis upon adoptive transfer. Taken together, these data indicate that it is the peripheral autoantigen itself that stimulates the generation of the appropriate regulatory cells from thymic emigrant precursors.<\/jats:p>","DOI":"10.1084\/jem.189.5.877","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:33Z","timestamp":1027702113000},"page":"877-882","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":207,"title":["Peripheral Autoantigen Induces Regulatory T Cells that Prevent Autoimmunity"],"prefix":"10.1084","volume":"189","author":[{"given":"Benedict","family":"Seddon","sequence":"first","affiliation":[{"name":"From the Medical Research Council Cellular Immunology Unit, Sir \u2009William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Don","family":"Mason","sequence":"additional","affiliation":[{"name":"From the Medical Research Council Cellular Immunology Unit, Sir \u2009William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1999,3,1]]},"reference":[{"key":"2023072508354159300_B1","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.1084\/jem.183.6.2669","article-title":"A critical role for transforming growth factor \u03b2 but not interleukin 4 in the suppression of T helper type 1\u2013mediated colitis by CD45RBlowCD4+T cells","volume":"183","author":"Powrie","year":"1996","journal-title":"J Exp Med"},{"key":"2023072508354159300_B2","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/39614","article-title":"A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis","volume":"389","author":"Groux","year":"1997","journal-title":"Nature"},{"key":"2023072508354159300_B3","first-page":"540","article-title":"Autoimmune oophoritis in thymectomized mice: detection of circulating antibodies against oocytes","volume":"40","author":"Taguchi","year":"1980","journal-title":"Clin Exp Immunol"},{"key":"2023072508354159300_B4","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1084\/jem.184.2.387","article-title":"Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation","volume":"184","author":"Asano","year":"1996","journal-title":"J Exp Med"},{"key":"2023072508354159300_B5","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/0167-5699(95)80089-1","article-title":"Post-thymectomy autoimmunity: abnormal T-cell homeostasis","volume":"16","author":"Bonomo","year":"1995","journal-title":"Immunol Today"},{"key":"2023072508354159300_B6","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/j.1600-065X.1996.tb00905.x","article-title":"The physiological role of regulatory T cells in the prevention of autoimmunity: the function of the thymus in the generation of the regulatory T cell subset","volume":"149","author":"Saoudi","year":"1996","journal-title":"Immunol Rev"},{"key":"2023072508354159300_B7","first-page":"362","article-title":"Thyroiditis in T cell-depleted rats. Influence of strain, radiation dose, adjuvants and antilymphocyte serum","volume":"21","author":"Penhale","year":"1975","journal-title":"Clin Exp Immunol"},{"key":"2023072508354159300_B8","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1084\/jem.177.3.627","article-title":"Evidence that the T cell repertoire of normal rats contains cells with the potential to cause diabetes. Characterization of the CD4+T cell subset that inhibits this autoimmune potential","volume":"177","author":"Fowell","year":"1993","journal-title":"J Exp Med"},{"key":"2023072508354159300_B9","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1084\/jem.184.6.2393","article-title":"The thymus contains a high frequency of cells that prevent autoimmune diabetes on transfer into pre-diabetic recipients","volume":"184","author":"Saoudi","year":"1996","journal-title":"J Exp Med"},{"key":"2023072508354159300_B10","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1084\/jem.189.2.279","article-title":"Regulatory T cells in the control of autoimmunity: the essential role of transforming growth factor \u03b2 and interleukin 4 in the prevention of autoimmune thyroiditis in rats by peripheral CD4+CD45RC\u2212 cells and CD4+CD8\u2212thymocytes","volume":"189","author":"Seddon","year":"1999","journal-title":"J Exp Med"},{"key":"2023072508354159300_B11","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1084\/jem.156.6.1577","article-title":"Study on cellular events in post-thymectomy autoimmune oophoritis in mice. II. Requirements of Lyt-1 cells in normal female mice for the prevention of oophoritis","volume":"156","author":"Sakaguchi","year":"1982","journal-title":"J Exp Med"},{"key":"2023072508354159300_B12","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1084\/jem.165.1.146","article-title":"Self tolerance and localized autoimmunity. Mouse models of autoimmune disease that suggest tissue-specific suppressor T cells are involved in self-tolerance","volume":"165","author":"Taguchi","year":"1987","journal-title":"J Exp Med"},{"key":"2023072508354159300_B13","doi-asserted-by":"crossref","first-page":"2928","DOI":"10.4049\/jimmunol.147.9.2928","article-title":"Effector and regulatory cells in autoimmune oophoritis elicited by neonatal thymectomy","volume":"147","author":"Smith","year":"1991","journal-title":"J Immunol"},{"key":"2023072508354159300_B14","doi-asserted-by":"crossref","first-page":"4227","DOI":"10.4049\/jimmunol.159.9.4227","article-title":"TCR-beta repertoire development in the mouse embryo","volume":"159","author":"Ema","year":"1997","journal-title":"J Immunol"},{"key":"2023072508354159300_B15","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1002\/eji.1830090603","article-title":"Identification of Ia glycoproteins in rat thymus and purification from rat spleen","volume":"9","author":"McMaster","year":"1979","journal-title":"Eur J Immunol"},{"key":"2023072508354159300_B16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bj1870001","article-title":"The kinetics of antibody binding to membrane antigens in solution and at the cell surface","volume":"187","author":"Mason","year":"1980","journal-title":"Biochem J"},{"key":"2023072508354159300_B17","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1002\/eji.1830100807","article-title":"Two subsets of rat T lymphocytes defined with monoclonal antibodies","volume":"10","author":"Brideau","year":"1980","journal-title":"Eur J Immunol"},{"key":"2023072508354159300_B18","first-page":"445","article-title":"A repopulation assay for B and T lymphocyte stem cells employing radiation chimaeras","volume":"14","author":"Hunt","year":"1981","journal-title":"Cell Tissue Kinet"},{"key":"2023072508354159300_B19","first-page":"319","article-title":"Acquisition of immunological self-recognition by the fetal rat","volume":"64","author":"Eishi","year":"1988","journal-title":"Immunology"},{"key":"2023072508354159300_B20","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1002\/eji.1830190806","article-title":"Interception of the development of self tolerance in fetal lambs","volume":"19","author":"McCullagh","year":"1989","journal-title":"Eur J Immunol"},{"key":"2023072508354159300_B21","first-page":"595","article-title":"Curtailment of autoimmunity following parabiosis with a normal partner","volume":"71","author":"McCullagh","year":"1990","journal-title":"Immunology"},{"key":"2023072508354159300_B22","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1002\/eji.1830260822","article-title":"Establishment of tissue-specific tolerance is driven by regulatory T cells selected by thymic epithelium","volume":"26","author":"Modigliani","year":"1996","journal-title":"Eur J Immunol"},{"key":"2023072508354159300_B23","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1038\/339622a0","article-title":"Tolerance of class I histocompatibility antigens expressed extrathymically","volume":"339","author":"Morahan","year":"1989","journal-title":"Nature"},{"key":"2023072508354159300_B24","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1093\/intimm\/7.5.715","article-title":"Mechanisms of immune tolerance induction through the thymic expression of a peripheral tissue-specific protein","volume":"7","author":"Antonia","year":"1995","journal-title":"Int Immunol"},{"key":"2023072508354159300_B25","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1006\/jaut.1998.0210","article-title":"Intrathymic expression of genes involved in organ specific autoimmune disease","volume":"11","author":"Heath","year":"1998","journal-title":"J Autoimmunity"},{"key":"2023072508354159300_B26","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/0092-8674(94)90169-4","article-title":"T cell receptor antagonist peptides induce positive selection","volume":"76","author":"Hogquist","year":"1994","journal-title":"Cell"},{"key":"2023072508354159300_B27","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1084\/jem.181.2.805","article-title":"Modulation of T cell development by an endogenous altered peptide ligand","volume":"181","author":"Hsu","year":"1995","journal-title":"J Exp Med"},{"key":"2023072508354159300_B28","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/1074-7613(95)90145-0","article-title":"Modulation of cytokine patterns of human autoreactive T cell clones by a single amino acid substitution of their peptide ligand","volume":"2","author":"Windhagen","year":"1995","journal-title":"Immunity"}],"container-title":["The Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/189\/5\/877\/1693092\/98-2127.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/189\/5\/877\/1693092\/98-2127.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T09:47:08Z","timestamp":1690278428000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/189\/5\/877\/7909\/Peripheral-Autoantigen-Induces-Regulatory-T-Cells"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,3,1]]},"references-count":28,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1999,3,1]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.189.5.877","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,3,1]]}}}