{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T08:38:44Z","timestamp":1770712724080,"version":"3.49.0"},"reference-count":0,"publisher":"Rockefeller University Press","issue":"6","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1996,6,1]]},"abstract":"<jats:p>Toxic shock syndrome (TSS) is a multi system disorder resulting from superantigen-mediated cytokine production. Nearly 90% of the clinical cases of TSS arise due to an exotoxin, toxic shock syndrome toxin-1 (TSST-1), elaborated by toxigenic strains of Staphylococcus aureus. It is clearly established that besides antigen-specific signals a variety of costimulatory signals are required for full T cell activation. However, the nature and potential redundancy of costimulatory signals are incompletely understood, particularly with regards to superantigen-mediated T cell activation in vivo. Here we report that CD28-deficient mice (CD28-\/-) are completely resistant to TSST-1-induced lethal TSS while CD28 (+\/-) littermate mice were partially resistant to TSST-1. The mechanism for the resistance of the CD28 (-\/-) mice was a complete abrogation of TNF-alpha accumulation in the serum and a nearly complete (90%) impairment of IFN-gamma secretion in response to TSST-1 injection. In contrast, the serum level of IL-2 was only moderately influenced by the variation of CD28 expression. CD28 (-\/-) mice retained sensitivity to TNF-alpha as demonstrated by equivalent lethality after cytokine injection. These findings establish an essential requirement for CD28 costimulatory signals in TSST-1-induced TSS. The hierarchy of TSST-1 resistance among CD28 wild-type (CD28+\/+), CD28 heterozygous (CD28+\/-), and CD28-\/- mice suggests a gene-dose effect, implying that the levels of T cell surface CD28 expression critically regulate superantigen-mediated costimulation. Finally, as these results demonstrate the primary and non-redundant role of CD28 receptors in the initiation of the in vivo cytokine cascade, they suggest therapeutic approaches for superantigen-mediated immunopathology.<\/jats:p>","DOI":"10.1084\/jem.183.6.2675","type":"journal-article","created":{"date-parts":[[2004,6,24]],"date-time":"2004-06-24T07:56:10Z","timestamp":1088063770000},"page":"2675-2680","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":53,"title":["Protection against lethal toxic shock by targeted disruption of the CD28 gene."],"prefix":"10.1084","volume":"183","author":[{"given":"B","family":"Saha","sequence":"first","affiliation":[{"name":"Naval Medical Research Institute, Bethesda, Maryland 20889, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D M","family":"Harlan","sequence":"additional","affiliation":[{"name":"Naval Medical Research Institute, Bethesda, Maryland 20889, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K P","family":"Lee","sequence":"additional","affiliation":[{"name":"Naval Medical Research Institute, Bethesda, Maryland 20889, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C H","family":"June","sequence":"additional","affiliation":[{"name":"Naval Medical Research Institute, Bethesda, Maryland 20889, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Abe","sequence":"additional","affiliation":[{"name":"Naval Medical Research Institute, Bethesda, Maryland 20889, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[1996,6,1]]},"container-title":["The Journal of experimental medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/183\/6\/2675\/1678401\/2675.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/183\/6\/2675\/1678401\/2675.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T07:12:16Z","timestamp":1690269136000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/183\/6\/2675\/21431\/Protection-against-lethal-toxic-shock-by-targeted"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,6,1]]},"references-count":0,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1996,6,1]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.183.6.2675","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,6,1]]}}}