Critical role of T cell migration in bacterial superantigen-mediated shock in mice

Bacterial superantigens have been implicated in the pathogenesis of several human diseases. Among them, toxic shock syndrome (TSS) is a prototypic acute intoxication caused by the pyrogenic exotoxin family of superantigens. In this study, we investigated the pathophysiological mechanism of TSS using the Yersinia pseudotuberculosis-derived mitogen (YPM) and its point mutants. The results indicated that YPM could induce toxic shock in BALB/c mice but not in T cell-deficient SCID mice. We found that Vbeta8(+) T cells activated by YPM migrated from peripheral blood to liver as early as 1 h after injection of YPM and that serum level of IFN-gamma was significantly elevated 4 h after YPM injection. Co-administration of anti-IFN-gamma antibody or anti-YPM monoclonal antibody alleviated the liver injury and protected mice from YPM-induced death. Moreover, anti-YPM antibody also suppressed the early migration of Vbeta8(+) T cells from the peripheral circulation and the elevation of serum IFN-gamma level, indicating a pivotal role of T cells in inducing shock in our mouse model. (C) 2004 Elsevier Inc. All rights reserved.