Superantigen shock in mice with an inapparent viral infection.
Subclinical lymphocytic choriomeningitis virus infection primes mice expressing a V beta 8.1D beta 2J beta 2.3C beta 2 T cell receptor as a transgene for induction of fatal hematogenous shock after administration of a dose of staphylococcal enterotoxin B (SEB) that is tolerated by uninfected controls. The lethal effect is greatly diminished by prior depletion of the virus-primed CD4+ T cells. Evidence of transient tumor necrosis factor (TNF) secretion is detected in serum within 1 h of SEB administration, and massive amounts of interferon-gamma (IFN-gamma) and interleukin-6 (IL-6) are present within 4-6 h. Mice are partly protected by treatment with dimeric soluble TNF receptor-Fc fusion protein or the nitric oxide synthase inhibitor, aminoguanidine, neither of which blocks SEB-induced IFN-gamma or IL-6 production. Administration of a monoclonal antibody to IFN-gamma concomitant with SEB effectively neutralizes this cytokine but has no effect on survival.
Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee.
S R
SR
Sarawar
M A
MA
Blackman
P C
PC
Doherty
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000097:blood; D004768:Enterotoxins / Q000633:toxicity*; D007376:Interleukin-2 / Q000096:biosynthesis; D008216:Lymphocytic Choriomeningitis / Q000150:complications*; D051379:Mice; D008808:Mice, Inbred CBA; D012772:Shock, Septic / Q000209:etiology* / Q000517:prevention & control; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000633:toxicity*
D016207:Cytokines; D004768:Enterotoxins; D007376:Interleukin-2; D018089:Superantigens; C031818:enterotoxin B, staphylococcal