Activation and re-activation potential of T cells responding to staphylococcal enterotoxin B

To elucidate the parameters that lead to superantigen inducednon-responsiveness, an in vitro model for studying primary andsecondary responses to the bacterial superantlgen staphylococcalenterotoxin B (SEB) was established. Upon re-activation withSEB, in vitro SEB primed T cells show an early proliferativeresponse that ‘quenches’ in time and is severelyimpaired 3 days after re-stimulatlon. Despite their overallimpaired proliferative capacity and IL-2 production, these Tcells are able to produce IFN-_ß and to up-regulateactivation markers CD69 and IL-2R upon re-stimulation with SEB,demonstrating that SEB non-responsiveness is not absolute. Rather,it reflects the inability to mount an ongoing proliferativeresponse upon re-stimulation with SEB. Our results also demonstratethat SEB-induced non-responsiveness is not simply the resultof presentation in the absence of co-stimulation, since presentationof SEB on highly purified dendritic cells during the primaryresponse did not prevent the induction of non-responsiveness.Aspreviously shown, SEB induces a T_h1 phenotype in respondingCD4⁺ T cells. Skewing towards a T_h2 phenotype by adding IL-4and antibodies to IFN-_ß did not prevent the inductionof non-responsiveness by SEB. Interestingly, T cells pretreatedwith plate-bound anti-CD3 and anti-V_ß8 were also non-responsiveto SEB re-stimulation. Thus, non-responsiveness to SEB (definedhere as inability to produce IL-2 and proliferate) seems toreflect an intrinsic inability of previously activated T cellsto respond to SEB, probably reflecting differences in signaltransduction pathways used by naive versus previously activatedT cells.