{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T14:46:32Z","timestamp":1761057992938},"reference-count":0,"publisher":"Rockefeller University Press","issue":"6","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1990,12,1]]},"abstract":"<jats:p>The lpr gene in homozygous form induces development of CD4-CD8-B220+ T cells and lymphadenopathy in MRL and C57BL\/6 mice. Although the propensity for excessive production of T cells is related to an intrinsic T cell defect, a thymus is also required because neonatal thymectomy eliminates lymphadenopathy. Recent evidence suggests that excessive production and release of autoreactive T cells from the thymus of lpr\/lpr mice might lead to downregulation of CD4 and CD8 as a \"fail safe\" tolerance mechanism that occurs during late thymic or post-thymic development. To test this hypothesis, T cell receptor (TCR) transgenic mice that produce large numbers of immature thymocytes recognizing the H-2Db and male H-Y antigens were backcrossed with C57BL\/6-lpr\/lpr mice and MRL-lpr\/lpr mice. It was predicted that Db male lpr\/lpr mice would produce large numbers of autoreactive T cells during early thymic development that would lead to an accelerated lymphoproliferative disease. In contrast, Db female lpr\/lpr mice would produce large numbers of Db H-Y-reactive T cells, but might not develop lymphadenopathy because the male H-Y antigen would not be present. Unexpectedly, there was complete elimination of lymphadenopathy in both male and female TCR transgenic lpr\/lpr mice. The elimination of lymphadenopathy was not due to a failure of thymic maturation since the thymus of H-2Db female lpr\/lpr mice contained nearly normal numbers of mature thymocytes. Elimination of lymphadenopathy was also not due to a lack of autoreactive T cells in the peripheral lymph nodes (LN) since there was an increased syngeneic mixed lymphocyte proliferative response of LNT cells from transgenic lpr\/lpr compared with +\/+ mice in vitro. Hypergammaglobulinemia and autoantibody production in the transgenic lpr\/lpr was present at levels comparable with or higher than control nontransgenic lpr\/lpr mice, suggesting a dissociation of autoantibody production from the lymphoproliferative disease in the TCR transgenic mice. Conversely, the development of lymphadenopathy and production of CD4-CD8-B220+ T cells appear to be intimately linked, as both were completely eliminated in T cells expressing the transgenic TCR. We propose that lymphoproliferation and production of CD4-CD8-6B2+ T cells in lpr\/lpr mice is related to decreased expression of the TCR, and providing the T cells with a rearranged TCR transgene overcomes this defect.<\/jats:p>","DOI":"10.1084\/jem.172.6.1805","type":"journal-article","created":{"date-parts":[[2004,6,24]],"date-time":"2004-06-24T07:56:10Z","timestamp":1088063770000},"page":"1805-1817","update-policy":"http:\/\/dx.doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":48,"title":["Transgenic rearranged T cell receptor gene inhibits lymphadenopathy and accumulation of CD4-CD8-B220+ T cells in lpr\/lpr mice."],"prefix":"10.1084","volume":"172","author":[{"given":"J D","family":"Mountz","sequence":"first","affiliation":[{"name":"University of Alabama, Department of Medicine, Birmingham 35294."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Zhou","sequence":"additional","affiliation":[{"name":"University of Alabama, Department of Medicine, Birmingham 35294."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Eldridge","sequence":"additional","affiliation":[{"name":"University of Alabama, Department of Medicine, Birmingham 35294."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Berry","sequence":"additional","affiliation":[{"name":"University of Alabama, Department of Medicine, Birmingham 35294."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Bl\u00fcthmann","sequence":"additional","affiliation":[{"name":"University of Alabama, Department of Medicine, Birmingham 35294."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[1990,12,1]]},"container-title":["The Journal of experimental medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/172\/6\/1805\/1671467\/1805.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/172\/6\/1805\/1671467\/1805.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T01:50:04Z","timestamp":1690249804000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/172\/6\/1805\/24786\/Transgenic-rearranged-T-cell-receptor-gene"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1990,12,1]]},"references-count":0,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1990,12,1]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.172.6.1805","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[1990,12,1]]}}}