T cell-mediated lethal shock triggered in mice by the superantigen staphylococcal enterotoxin B: critical role of tumor necrosis factor.
Because mice are more resistant than humans to the pathogenic effects of bacterial toxins, we used D-Galactosamine- (D-Gal) sensitized mice as a model system to evaluate potential toxic shock symptoms triggered by the superantigen staphylococcal enterotoxin B (SEB). We show that similar to endotoxin (lipopolysaccharide) [LPS], the exotoxin SEB causes lethal shock within 8 h in D-Gal-sensitized mice, inducing 100% and about 50% lethality with 20 and 2 micrograms SEB, respectively. The lethal shock triggered by the superantigen SEB is mediated by T cells, a conclusion based on the observation that T cell repopulation of SCID mice conferred sensitivity to SEB. Since CSA also conferred protection, the role of T cell-derived lymphokines in mediating lethal shock was evaluated. Within 30-60 min after SEB injection, serum tumor necrosis factor (TNF) levels peaked, followed immediately by interleukin-2 (IL-2). Serum-borne lymphokines were detected well in advance of signs of T cell activation, as assessed by IL-2 receptor expression of SEB-reactive V beta 8+ T cells. Passive immunization with anti-TNF-alpha/beta-neutralizing monoclonal antibody also conferred protection, indicating that it is TNF which is critical for initiating toxic shock symptoms. Taken together, this study defines basic differences between endotoxin (LPS)- and exotoxin (SEB)-mediated lethal shock, in that the former is mediated by macrophages and the latter by T cells. Yet the pathogenesis distal to the lymphokine/cytokine-producing cells appears surprisingly similar in that TNF represents a key mediator in inducing shock.
Miethke
T
T
Institute of Medical Microbiology and Hygiene, Technischen, Universität Munich, Germany.
Wahl
C
C
Heeg
K
K
Echtenacher
B
B
Krammer
P H
PH
Wagner
H
H
D000818:Animals; D002478:Cells, Cultured; D003643:Death; D004768:Enterotoxins / Q000633:toxicity*; D005434:Flow Cytometry; D005688:Galactosamine / Q000633:toxicity; D007376:Interleukin-2 / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D012772:Shock, Septic / Q000097:blood / Q000276:immunology*; D013211:Staphylococcus aureus; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D004768:Enterotoxins; D007376:Interleukin-2; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C031818:enterotoxin B, staphylococcal; D005688:Galactosamine