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.
Anderson
M R
MR
The Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4943, USA.
Tary-Lehmann
M
M
D000818:Animals; D004198:Disease Susceptibility / Q000503:physiopathology*; D004768:Enterotoxins / Q000494:pharmacology*; D007113:Immunity, Innate; D051379:Mice; D008806:Mice, Inbred AKR; D008809:Mice, Inbred C3H; D008808:Mice, Inbred CBA; D012772:Shock, Septic / Q000139:chemically induced* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D004768:Enterotoxins; D014409:Tumor Necrosis Factor-alpha; C031818:enterotoxin B, staphylococcal