Journal
IMMUNOLOGY LETTERS
Volume 82, Issue 1-2, Pages 75-78Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0165-2478(02)00021-4
Keywords
superantigen; interleukin-2 gene induction; interferon-gamma gene induction; gene expression shutoff
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Superantigens, exemplified by staphylococcal enterotoxin B (SEB), are the strongest known inducers of a cellular immune response; they elicit the production of excessive amounts of Th 1 cytokines, IL-2, IFN-gamma and TNF, leading to toxic shock. We show that increasing doses of SEB cause not only a greater induction but also a more rapid cessation of IL-2 gene expression. Remarkably, exposure of human PBMC to a second dose of SEB, even at concentrations 10- or 100-fold lower than the initial inducing dose and even within 2 h after the first exposure to SEB, resulted in an immediate and essentially complete shutoff of the induced IL-2 and IFN-gamma mRNA expression. The shutoff response was observed when primary induction of IL-2 and IFN-gamma gene expression was by SEB but not when it was by phytohemaggutinin-P. Signaling by a superantigen thus results not only in a vigorous induction of Th 1 cytokine genes but concomitantly induces the ability to shut off their expression upon re-exposure to superantigen. Without induction of this negative control mechanism, the cellular immune response to a superantigen would be even more pronounced. (C) 2002 Elsevier Science B.V. All rights reserved.
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