Toxic Shock Syndrome Toxin-1, Toxic Shock, and the Immune System

Toxic shock syndrome (TSS) is a severe multisystem disorder characterized by high fever, hypotension, generalized erythroderma, desquamation of the skin, and dysfunction of multiple organ systems (Chesney 1989; Davis et al. 1980; Todd et al. 1978). TSS is consistently associated with infection by toxigenic strains of Staphylococcus aureus, most commonly in the setting of tampon use during menses or following surgery or trauma. Exotoxins secreted by staphylococcal isolates from patients with TSS, most notably toxic shock syndrome toxin-1 (TSST-1), but also the structurally related staphylococcal enterotoxins, play a key role in the pathophysiology of this disease. It has been recently appreciated that the toxicity of TSST-1 stems from its ability to initiate uncontrolled activation of large numbers of immune cells by virtue of its capacity to bind MHC class II (la) molecules (Scholl et al. 1989a; Uchiyama et al. 1989a). Once bound to la molecules, TSST-1 can transmit activation signals to la+ immune cells including monocytes, B lymphocytes, activated T lymphocytes, and activated natural killer cells. At the same time, la-bound TSST-1 acts as a superantigen that interacts with and activates human T lymphocytes whose T cell receptor β chains bear a particular variable (V) gene sequence, Vβ2 (Choi et al. 1989). In this review, we will focus on the characteristics of the interaction between TSST-1 and la molecules and on the functional consequences of superantigen formation, including Vβ-restricted activation of T lymphocytes and superantigen-mediated cognate T/B cell interaction. We will also examine evidence for the induction by TSST-1 of transmembrane signals via la molecules that regulate intercellular adhesion interactions mediated by lymphocyte function-associated molecule 1 (LFA-1; CD11 a/CD18), T and B lymphocyte activation, and monokine gene transcription. Finally, we will discuss the relevance of the interaction of TSST-1 with la molecules to the pathophysiology of TSS.