Staphylococcal enterotoxin-B-induced lethal shock in mice is T-cell-dependent, but disease susceptibility is defined by the non-T-cell compartment.

Here we introduce a murine model for SEB-induced lethal shock that relies on the administration of SEB alone and does not involve hepatotoxicity by avoiding pretreatment with the hepatotoxin D-galactosamine. In the absence of D-gal, we first identified SEB-susceptible and -resistant H-2(k)-congenic mouse strains. In contrast with what is well established for the classic D-gal-dependent model and what therefore is anticipated for the human disease, the levels of TNF produced did not define susceptibility in our model. The SEB-induced TNF response in vitro and in vivo was stronger in resistant B10.BR mice than in susceptible C3H/HeJ mice. Neither the magnitude nor the quality of the T cell response induced by SEB defined susceptibility. Adoptive transfer experiments in C3H-SCID recipient mice demonstrated that induction of the disease is T-cell-dependent. T cells from resistant and susceptible mice both transferred disease susceptibility to H-2(k)-congenic C3H-SCID mice, indicating that disease susceptibility is downstream from T cell activation, at the level of the target organ itself, which responds differently to T-cell-induced inflammation. Copyright 2001 Academic Press.