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Tolerance could be obtained without Tcell depletion across multiple minor antigen mismatches, both in naive and primed animals, demonstrating that peripheral T cells could be tolerized, even if they had been previously activated. Where donor and recipient were incompatible across the whole major histocompatibility complex, specific tolerance could be achieved by using a combination of depleting followed by non\u2010depleting antibodies, where each alone was unsuccessful. Although mice clearly tolerated their original skin grafts, we observed in some strain combinations that a second fresh, but genotypically identical graft, was slowly rejected. Such mice also possessed Tcells which could proliferate to donor\u2010type stimulator cells in <jats:italic>vitro<\/jats:italic>. Whatever the mechanisms, we have demonstrated that operational transplantation tolerance can be achieved with simple, non\u2010toxic antibody therapy. The introduction of comparable tolerance\u2010inducing regimens in clinical organ transplantation could obviate the need for long\u2010term immunosuppression and its unfortunate side effects.<\/jats:p>","DOI":"10.1002\/eji.1830201232","type":"journal-article","created":{"date-parts":[[2007,3,1]],"date-time":"2007-03-01T11:54:29Z","timestamp":1172750069000},"page":"2747-2755","source":"Crossref","is-referenced-by-count":115,"title":["The induction of skin graft tolerance in major histocompatibility complex\u2010mismatched or primed recipients: primed T cells can be tolerized in the periphery with anti\u2010CD4 and anti\u2010CD8 antibodies"],"prefix":"10.1002","volume":"20","author":[{"given":"Stephen P.","family":"Cobbold","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilly","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herman","family":"Waldmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,12,14]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/172603a0"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-198610000-00018"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.146.1.34"},{"key":"e_1_2_1_5_2","first-page":"147","volume-title":"Cell Biology","author":"Cobbold S. 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