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T lymphocytes from these animals react to minute amounts (10\u2013100 times less than control mice) of staphylococcal enterotoxin B (SEB) <jats:italic>in vitro<\/jats:italic>, similar to concentrations to which human cells react. <jats:italic>In vivo<\/jats:italic>, these double\u2010transgenic, double\u2010knockout mice succumb to normally sublethal amounts of SEB. This sensitivity is not due to a biased T cell receptor V\u03b2 repertoire, increased T cell reactivity, or increased sensitivity to macrophage\u2010derived cytokines. Rather, tumor necrosis factor (TNF)\u2010\u03b1 production by T cells and serum levels of TNF\u2010\u03b1 correlate precisely with the clinical syndrome, showing a biphasic T cell\u2010dependent response. These data show that both human CD4 and MHC class II molecules can render mice supersensitive to superantigen\u2010induced septic shock syndrome. This animal model mimics the progression of septic shock in man by transforming normally resistant mice into hypersensitive SEB responders, a trait that is characteristic of humans. Mice that have been humanized by exchanging autochthonous superantigen ligands by their human equivalents may be useful to decipher superantigen responses <jats:italic>in vivo<\/jats:italic> and to assess the pathogenesis of superantigen\u2010associated diseases.<\/jats:p>","DOI":"10.1002\/eji.1830260518","type":"journal-article","created":{"date-parts":[[2007,3,2]],"date-time":"2007-03-02T02:03:19Z","timestamp":1172800999000},"page":"1074-1082","source":"Crossref","is-referenced-by-count":43,"title":["Human CD4 and human major histocompatibility complex class II (DQ6) transgenic mice: supersensitivity to superantigen\u2010induced septic shock"],"prefix":"10.1002","volume":"26","author":[{"given":"Rae S. 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