Staphylococcal Superantigen (TSST-1) Mutant Analysis Reveals that T Cell Activation Is Required for Biological Effects in the Rabbit Including the Cytokine Storm 英文参考文献.docVIP

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Staphylococcal Superantigen (TSST-1) Mutant Analysis Reveals that T Cell Activation Is Required for Biological Effects in the Rabbit Including the Cytokine Storm 英文参考文献.doc

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Staphylococcal Superantigen (TSST-1) Mutant Analysis Reveals that T Cell Activation Is Required for Biological Effects in the Rabbit Including the Cytokine Storm 英文参考文献

Toxins 2010, 2, 2272-2288; doi:10.3390/toxins2092272 OPEN ACCESS toxins ISSN 2072-6651 /journal/toxins Article Staphylococcal Superantigen (TSST-1) Mutant Analysis Reveals that T Cell Activation Is Required for Biological Effects in the Rabbit Including the Cytokine Storm Norbert Stich 1, Martina Waclavicek 1, Nina Model 1 and Martha M. Eibl 1,2,* 1 Biomedizinische ForschungsgmbH Lazarettgasse 19/2, A-1090 Vienna, Austria; E-Mails: Norbert.Stich@biomed-research.at (N.S.); Martina.Waclavicek@biomed-research.at (M.W.); Nina.Model@biomed-research.at (N.M.) 2 Immunology Outpatient Clinic, Schwarzspanierstrasse 15, A-1090 Vienna, Austria * Author to whom correspondence should be addressed; E-Mail: martha.eibl@meduniwien.ac.at; Tel.: +43-1-4081091-11; Fax: +43-1-4081091-13. Received: 2 August 2010; in revised form: 1 September 2010 / Accepted: 7 September 2010 / Published: 9 September 2010 Abstract: Staphylococcal superantigens (sAgs), such as toxic shock syndrome toxin 1 (TSST-1), induce massive cytokine production, which may result in toxic shock syndrome (TSS) and sepsis. Recently, we reported that in vitro studies in human peripheral blood mononuclear cells (PBMC) do not reflect the immunological situation of the host, because after exposure to superantigens (sAgs) in vivo, mononuclear cells (MNC) leave the circulation and migrate to organs, e.g., the spleen, liver and lung. Our experimental model of choice is the rabbit because it is comparable to humans in its sensitivity to sAg. T cell activation has been assessed by lymphocyte proliferation and IL-2 gene expression after in vivo challenge with TSST-1 and the mutant antigens; expression of the genes of proinflammatory cytokines were taken as indicators for the inflammatory reaction after the combined treatment with TSST-1 and LPS. The question as to whether the biological activities of TSST-1, e.g., lymphocyte extravasation, toxicity