Superantigen concomitantly induces Th1 cytokine genes and the ability to shut off their expression on re-exposure to superantigen.
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 Th1 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 Th1 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.
Arad
Gila
G
Department of Molecular Virology, Hadassah Medical School, The Hebrew University of Jerusalem, Jerusalem, Israel.
Levy
Revital
R
Kaempfer
Raymond
R
D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D004768:Enterotoxins / Q000276:immunology*; D020868:Gene Silencing; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D007700:Kinetics; D012333:RNA, Messenger / Q000096:biosynthesis; D018089:Superantigens / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D015533:Transcriptional Activation
D004768:Enterotoxins; D007376:Interleukin-2; D012333:RNA, Messenger; D018089:Superantigens; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma