{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T01:47:00Z","timestamp":1777945620261,"version":"3.51.4"},"reference-count":0,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2008,10,8]],"date-time":"2008-10-08T00:00:00Z","timestamp":1223424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2008,10,8]],"date-time":"2008-10-08T00:00:00Z","timestamp":1223424000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathobiology"],"abstract":"<jats:p>Recombinant toxic shock syndrome toxin-1 (rTSST-1) administered to MRL-Ipr\/lprLCR V\u03b28.2 transgenic mice at doses of 0.1 \u00b5g\/mouse resulted in 100% mortality. This was an unexpected finding since TSST-1 does not activate V\u03b28.2 T cells. In contrast, control mice heterozygous at the Ipr locus and also for the transgene (MRL-lpr\/+\u00b7, V\u03b28.2\/0) survived doses of superantigen 100 times higher. The transgenic mice which succumbed to rTSST-1 challenge exhibited histopathology of the liver consistent with toxic shock (generalized inflammation and hepatocellualr necrosis) as well as substantially elevated serum TNF-\u03b1, IL-2, and IL\u00b76 cytokine levels. Splenic T cells derived from transgenic mice stimulated with rTSST-1 in vitro did not undergo detectable proliferation as measured in a standard mitogen assay. However, PCR amplification of cDNA prepared from the V\u03b28.2 splenocytes revealed the presence of minor populations of TSST-1 -reactive V\u03b2 elements (i.e. V\u03b23 and V\u03b2l5). Furthermore, an expansion of the V\u03b23 and V\u03b2l5 T-cell families was detected by PCR assay of spleen cell cultures stimulated with rTSST-1. These results suggested that the exquisite sensitivity of the MRL-lpr\/lpr V\u03b28.2 transgenic animals to rTSST-1 was not dependent exclusively on T-cell proliferation but was augmented by the influence of a defective fas antigen receptor expressed in homozygous Ipr mice. To test this hypothesis more directly, we compared the sensitivity of MRL-lpr\/lpr mice (not carrying the V\u03b28.2 transgene) to MRL\u00b7+\/+ mice. The MRL-lpr\/lpr fas antigen-defective mice were substantially more susceptible to rTSST-1 challenge. Mice carrying the Ipr mutation on another genetic background (C51BL\/6.C3H-lpr\/lpr) were also more sensitive to rTSST-1 challenge than were C57BL\/6.C3H-+\/+ mice. Although induction of toxic shock is clearly associated with T-cell proliferation, defects in fas antigen receptor or ligand may also contribute substantively to superantigen-mediated lethal shock by still undefined mechanisms.<\/jats:p>","DOI":"10.1159\/000163965","type":"journal-article","created":{"date-parts":[[2008,10,20]],"date-time":"2008-10-20T03:39:40Z","timestamp":1224473980000},"page":"293-304","source":"Crossref","is-referenced-by-count":3,"title":["A fas Antigen Receptor Mutation Allows Development of Toxic Shock Syndrome Toxin-1 -Induced Lethal Shock in V\u03b28.2T-Cell Receptor Transgenic Mice"],"prefix":"10.1159","author":[{"given":"Constance M.","family":"Cullen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter F.","family":"Bonventre","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holly","family":"Heeg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Horst","family":"Bluethmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John D.","family":"Mountz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carl K.","family":"Edwards, III","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2008,10,8]]},"container-title":["Pathobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/000163965","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T12:38:39Z","timestamp":1777725519000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000163965"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,10,8]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1159\/000163965","archive":["Portico"],"relation":{},"ISSN":["1015-2008","1423-0291"],"issn-type":[{"value":"1015-2008","type":"print"},{"value":"1423-0291","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,10,8]]}}}