ACTIVATION AND REACTIVATION POTENTIAL OF T-CELLS RESPONDING TO STAPHYLOCOCCAL-ENTEROTOXIN-B

To elucidate the parameters that lead to superantigen induced non-resp onsiveness, an in vitro model for studying primary and secondary respo nses to the bacterial superantigen staphylococcal enterotoxin B (SEB) was established. Upon re-activation with SEB, in vitro SEB primed T ce lls show an early proliferative response that 'quenches' in time and i s severely impaired 3 days after re-stimulation, Despite their overall impaired proliferative capacity and IL-2 production, these T cells ar e able to produce IFN-gamma and to up-regulate activation markers CD69 and IL-2R alpha upon re-stimulation with SEB, demonstrating that SEB non-responsiveness is not absolute. Rather, it reflects the inability to mount an ongoing proliferative response upon re-stimulation with SE B. Our results also demonstrate that SEB-induced non-responsiveness is not simply the result of presentation in the absence of co-stimulatio n, since presentation of SEB on highly purified dendritic cells during the primary response did not prevent the induction of non-responsiven ess. As previously shown, SEB induces a T(h)1 phenotype in responding CD4(+) T cells. Skewing towards a T(h)2 phenotype by adding IL-4 and a ntibodies to IFN-gamma did not prevent the induction of nonresponsiven ess by SEB. Interestingly, T cells pretreated with plate-bound anti-CD 3 epsilon and anti-V(beta)8 were also non-responsive to SEB re-stimula tion. Thus, non-responsiveness to SEB (defined here as inability to pr oduce IL-2 and proliferate) seems to reflect an intrinsic inability of previously activated T cells to respond to SEB, probably reflecting d ifferences in signal transduction pathways used by naive versus previo usly activated T cells.