STAPHYLOCOCCAL-ENTEROTOXIN-B INDUCES AN EARLY AND TRANSIENT STATE OF IMMUNOSUPPRESSION CHARACTERIZED BY V-BETA-UNRESTRICTED T-CELL UNRESPONSIVENESS AND DEFECTIVE ANTIGEN-PRESENTING CELL FUNCTIONS

Staphylococcal enterotoxin B (SEB) is a bacterial enterotoxin able to simultaneously bind to class II molecules on APCs and to selected V be ta regions (including V beta 8) of the TCR complex. Administration of SEB to adult BALB/c mice results in clonal activation of T cells beari ng V beta 8 receptors, leading to an excessive release of proinflammat ory cytokines. This initial immune response is followed by a long-last ing state of V beta 8-specific unresponsiveness, thought to benefit bo th the host (as it contributes to the down-regulation of the inflammat ory response) and the bacterium (through ligand-specific T cell anergy ). However, it is not clear how this type of restricted unresponsivene ss can effectively impair the generation of an antibacterial response. To gain insight into the mechanism by which Gram-positive bacteria su bvert the host immune response, we have investigated the immune compet ence of SEB-treated mice 48 h following SEB administration. We demonst rate in this report that in vivo, SEB induces a transient but profound state of unresponsiveness affecting both T and Ag-presenting cell fun ctions. Although in vivo activation by SEB appears to be V beta-restri cted under our experimental conditions, SEB-treated mice displayed an early (lasting 48 to 72 h postinjection) and V beta-unrestricted unres ponsive state characterized by the inability to produce IL-2 in respon se to polyclonal TCR mitogens including third party bacterial superant igens (staphylococcal enterotoxin A and toxic shock syndrome toxin 1, SEA and TSST-1, respectively), Abs to non-SEB reactive V beta regions (V beta 6), anti-CD3 epsilon Abs, and a lectin (Con A). Spleen cell po pulations from SEB-treated mice also displayed defective APC functions , possibly related to a selective decrease in splenic dendritic cells numbers. Taken together, these observations indicate that SEB induces an early and transient state of immunodeficiency in vivo, representing a potential mechanism for escaping host immune surveillence.