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

Excessive T cell activation induced by bacterial superantigens plays an important role in the pathology associated with Gram-positive bacteremia. To gain insight into the early phases of T cell activation by bacterial enterotoxins in vivo, we investigated the ability of antibodies to well-defined co-stimulatory molecules to inhibit T cell activation and the subsequent toxic shock syndrome induced in BALB/c mice following the injection of staphylococcal enterotoxin B (SEE). We demonstrate here that a single dose of anti-B7.2 antibodies, but not anti-B7.1 antibodies, significantly inhibits T cell activation, as judged by lower systemic IL-2 release, blastogenesis and IL-2 receptor expression, and reduces the lethal effect of SEE in D-galactosamine-sensitized mice. These results demonstrate that co-stimulation through the B7.2 molecule plays an important role in the activation of T cells in response to SEE in vivo and suggest alternative therapies for septic shock caused by bacterial enterotoxins based on blocking antibodies to co-stimulatory molecules.