Pathogenesis of the toxic shock syndrome: T cell mediated lethal shock caused by the superantigen TSST‐1

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Abstract
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.