{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:42:53Z","timestamp":1781109773200,"version":"3.54.1"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1991,12,15]]},"abstract":"<jats:p>To investigate tolerance to extrathymic self molecules, we produced two groups of transgenic mice: one expressed the major histocompatibility complex molecule H-2Kb in pancreatic beta cells, and the other expressed rearranged T-cell receptor genes encoding an anti-H-2Kb receptor. The transgenic T-cell receptor genes were shown to confer the correct specificity and to be expressed appropriately. T cells bearing this receptor were activated by H-2Kb in vitro and in vivo, and they underwent negative selection in mice expressing H-2Kb in the thymus. To determine the fate and function of these anti-H-2Kb T cells in mice expressing H-2Kb exclusively in the periphery, the two groups of transgenic mice were mated to produce double transgenic offspring. In these, transgene-expressing T cells were present in both thymus and periphery. Persisting T cells had not down-regulated either their antigen-specific receptors or their CD8 molecules. Despite the persistence of large numbers of potentially reactive T cells, the mice were tolerant of H-2Kb in that they could not reject H-2Kb-bearing skin grafts, although they did reject third-party grafts. The results show that peripheral T-cell tolerance, unlike that imposed in the thymus, does not involve deletion of T cells. The existence of T cells bearing receptors specific for self components raises the possibility that aberrant activation of such cells may lead to the development of autoimmune disease.<\/jats:p>","DOI":"10.1073\/pnas.88.24.11421","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T07:52:00Z","timestamp":1149061920000},"page":"11421-11425","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":22,"title":["A nondeletional mechanism of peripheral tolerance in T-cell receptor transgenic mice."],"prefix":"10.1073","volume":"88","author":[{"given":"G","family":"Morahan","sequence":"first","affiliation":[{"name":"Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M W","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J F","family":"Miller","sequence":"additional","affiliation":[{"name":"Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1991,12,15]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.88.24.11421","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T13:23:32Z","timestamp":1649856212000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.88.24.11421"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1991,12,15]]},"references-count":0,"journal-issue":{"issue":"24","published-print":{"date-parts":[[1991,12,15]]}},"alternative-id":["10.1073\/pnas.88.24.11421"],"URL":"https:\/\/doi.org\/10.1073\/pnas.88.24.11421","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1991,12,15]]},"assertion":[{"value":"1991-12-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}