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Such tolerance is antigen-specific, mediated by regulatory T cells, and can be extended through linked suppression to na\u00efve lymphocytes. The same protocol, when combined with allogeneic bone marrow, enables the development of mixed hematopoietic chimerism and deletional tolerance. Although we cannot exclude that some regulatory T cells may persist in chimeric mice, these cells are insufficient to mediate linked suppression. CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup>T cells, whether taken from na\u00efve mice or from mice tolerized through either treatment protocol, were always able to prevent rejection of skin grafts by na\u00efve CD4<jats:sup>+<\/jats:sup>T cells, and did so with no demonstrable specificity for the tolerizing donor antigens. Such data question whether CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup>regulatory T cells alone can account for the antigen specificity of dominant transplantation tolerance.<\/jats:p>","DOI":"10.1073\/pnas.0400084101","type":"journal-article","created":{"date-parts":[[2004,6,25]],"date-time":"2004-06-25T00:25:50Z","timestamp":1088123150000},"page":"10122-10126","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":88,"title":["Donor-specific transplantation tolerance: The paradoxical behavior of CD4<sup>+<\/sup>CD25<sup>+<\/sup>T cells"],"prefix":"10.1073","volume":"101","author":[{"given":"Luis","family":"Graca","sequence":"first","affiliation":[{"name":"Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom"}]},{"given":"Alain","family":"Le Moine","sequence":"additional","affiliation":[{"name":"Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom"}]},{"given":"Chun-Yen","family":"Lin","sequence":"additional","affiliation":[{"name":"Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom"}]},{"given":"Paul J.","family":"Fairchild","sequence":"additional","affiliation":[{"name":"Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom"}]},{"given":"Stephen P.","family":"Cobbold","sequence":"additional","affiliation":[{"name":"Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom"}]},{"given":"Herman","family":"Waldmann","sequence":"additional","affiliation":[{"name":"Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom"}]}],"member":"341","published-online":{"date-parts":[[2004,6,24]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80856-9"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri821"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni0901-816"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1027"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"4805","DOI":"10.4049\/jimmunol.163.9.4805","volume":"163","year":"1999","unstructured":"Honey, K., Cobbold, S. 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