T-CELL ANERGY IS PROGRAMMED EARLY AFTER EXPOSURE TO BACTERIAL SUPERANTIGEN IN-VIVO

We have investigated the effects of the protein synthesis inhibitor, cycloheximide (CHX), on the induction of post-thymic T cell tolerance in mice primed with the bacterial superantigen, Staphylococcus aureus enterotoxin B (SEB). A single injection of 1 mg CHX prevented protein synthesis in splenic cells for <6 h in vivo. The concomitant administration of SEB and CHX prevented induction of SEB-specific anergy, but did not interfere with the deletion of SEB-specific V(beta)8+ T cells by activation-induced, programmed cell death. When CHX was given greater-than-or-equal-to 24 h after SEB administration the expression of anergy was not affected. These findings suggest that anergy and deletion represent independent processes. Furthermore, these observations, together with the fact that SEB retains the potential to induce anergy in specific T cells 8 h after priming in vivo, imply that the determination of alternate fates (anergy or death) occurs at early time points after SEB injection.