Role of T cells and gamma interferon during induction of hypersensitivity to lipopolysaccharide by toxic shock syndrome toxin 1 in mice.
The superantigenic function of toxic shock syndrome toxin 1 (TSST-1) is generally regarded as an important determinant of its lethal effects in humans or experimental animals. This study examined the role of superantigenicity in a BALB/c mouse model of lethal TSST-1-induced hypersensitivity to lipopolysaccharide (LPS). In this model, TSST-1 greatly potentiated both LPS-induced lethality, as well as LPS-induced serum tumor necrosis factor alpha (TNF-alpha) activity. Although BALB/c-SCID mice were resistant to these LPS enhancement effects of TSST-1, BALB/c-SCID mice reconstituted with T cells were completely susceptible to the enhancement effect of TSST-1 on LPS-induced serum TNF-alpha. Mice pretreated with cyclosporine (Cs) or neutralizing antibodies against gamma interferon (IFN-gamma) did not develop lethal LPS hypersensitivity when injected with TSST-1, and these agents reduced the enhancement effect of TSST-1 on LPS-induced serum TNF-alpha by 99 and 85%, respectively. Cs pretreatment also completely inhibited the known capacity of TSST-1 to amplify LPS-induced levels of IFN-gamma in serum. In contrast, mice given Cs after a priming injection of TSST-1, but before LPS, still exhibited lethal hypersensitivity to LPS. Cs given after TSST-1 also did not inhibit enhancement of LPS-induced serum TNF-alpha by TSST-1 but inhibited the enhancement effect of TSST-1 on LPS-induced serum IFN-gamma by 50%. These experiments support the theory that TSST-1-induced hypersensitivity to LPS is mediated primarily by IFN-gamma derived from superantigen-activated T cells.
Dinges
M M
MM
Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
Schlievert
P M
PM
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001427:Bacterial Toxins; D016572:Cyclosporine / Q000494:pharmacology; D004768:Enterotoxins / Q000276:immunology*; D005260:Female; D006967:Hypersensitivity / Q000209:etiology* / Q000401:mortality; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology*; D017710:Lymphocyte Transfusion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D018089:Superantigens / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins; D004768:Enterotoxins; D008070:Lipopolysaccharides; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C030107:enterotoxin F, Staphylococcal; D007371:Interferon-gamma; D016572:Cyclosporine