B7.2 provides co-stimulatory 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 (SEB). 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 SEB 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 SEB in vivo and suggest alternative therapies for septic shock caused by bacterial enterotoxins based on blocking antibodies to co-stimulatory molecules.
Muraille
E
E
Département de Biologie Moléculaire, Université Libre de Bruxelles, Rhode-St-Genèse, Belgium.
De Smedt
T
T
Urbain
J
J
Moser
M
M
Leo
O
O
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD; D018122:B7-1 Antigen / Q000502:physiology*; D051940:B7-2 Antigen; D017635:Clonal Anergy; D004768:Enterotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D005260:Female; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D004768:Enterotoxins; D008562:Membrane Glycoproteins; C031818:enterotoxin B, staphylococcal