B7.2 PROVIDES COSTIMULATORY FUNCTIONS IN-VIVO IN RESPONSE TO STAPHYLOCOCCAL-ENTEROTOXIN-B

Excessive T cell activation induced by bacterial superantigens plays a n important role in the pathology associated with Gram-positive bacter emia. To gain insight into the early phases of T cell activation by ba cterial enterotoxins in vivo, we investigated the ability of antibodie s to well-defined co-stimulatory molecules to inhibit T cell activatio n and the subsequent toxic shock syndrome induced in BALB/c mice follo wing the injection of staphylococcal enterotoxin B (SEE). We demonstra te here that a single dose of anti-B7.2 antibodies, but not anti-B7.1 antibodies, significantly inhibits T cell activation, as judged by low er systemic IL-2 release, blastogenesis and IL-2 receptor expression, and reduces the lethal effect of SEE in D-galactosamine-sensitized mic e. These results demonstrate that co-stimulation through the B7.2 mole cule plays an important role in the activation of T cells in response to SEE in vivo and suggest alternative therapies for septic shock caus ed by bacterial enterotoxins based on blocking antibodies to co-stimul atory molecules.