SUPERANTIGEN SHOCK IN MICE WITH AN INAPPARENT VIRAL-INFECTION

Subclinical lymphocytic choriomeningitis virus infection primes mice e xpressing 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 administrati on of a dose of staphylococcal enterotoxin B (SEB) that is tolerated b y uninfected controls. The lethal effect is greatly diminished by prio r 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-ga mma) and interleukin-6 (IL-6) are present within 4-6 h. Mice are partl y protected by treatment with dimeric soluble TNF receptor-Fc fusion p rotein or the nitric oxide synthase inhibitor, aminoguanidine, neither of which blocks SEE-induced IFN-gamma or IL-6 production. Administrat ion of a monoclonal antibody to IFN-gamma concomitant with SEB effecti vely neutralizes this cytokine but has no effect on survival.