Pathogenesis of the toxic shock syndrome: T cell mediated lethal shock caused by the superantigen TSST-1.
The pathogenesis of the toxic shock syndrome (TSS) is only incompletely understood. We now present evidence that TSS toxin-1 (TSST-1), one of the superantigens produced by Staphylococcus aureus, induces lethal shock in D-galactosamine sensitized mice. In this model TSS is dependent on T cells, since cyclosporin A (CsA) completely blocked development of shock, and since T cell-deficient SCID mice did not show signs of disease upon injection with TSST-1. However, SCID mice repopulated with T cells succumbed to lethal shock. The disease is characterized by a burst of lymphokines like interleukin-2 (IL-2) and tumor necrosis factor (TNF) released into the sera of TSST-1-treated animals. Already 1-2 h after TSST-1 application TNF serum levels peaked and IL-2 levels peaked around 4 h after treatment. TNF appears as key mediator of TSS, because anti-TNF monoclonal antibodies protected TSST-1-challenged mice. Interestingly, the burst of TNF in serum was noted well in advance of detectable markers of T cell activation. Thus, about 5% of all peripheral T cells started to express the IL-2 receptors as late as 4 h after treatment. Comparing TSST-1- and endotoxin-induced shock we conclude that TNF effects shock in both diseases. However, the type of cells involved appears distinct in that T cells cause TSS triggered by the exotosin TSST-1 while macrophages mediate the shock induced by endotoxins.
Miethke
T
T
Institute of Medical Microbiology and Hygiene Technical University of Munich, FRG.
Duschek
K
K
Wahl
C
C
Heeg
K
K
Wagner
H
H
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001427:Bacterial Toxins; D004768:Enterotoxins / Q000276:immunology*; D005688:Galactosamine / Q000276:immunology; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000097:blood; D008233:Lymphotoxin-alpha / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D012772:Shock, Septic / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D004768:Enterotoxins; D008222:Lymphokines; D008233:Lymphotoxin-alpha; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C030107:enterotoxin F, Staphylococcal; D005688:Galactosamine