Staphylococcal enterotoxin B modulates V beta 8+ TcR-associated T-cell memory against conventional antigen.

Primary in vivo challenge with the superantigen staphylococcal enterotoxin B (SEB) induces polyclonal proliferation of an unusually large proportion of circulating T-cells that bear the V beta 8-T-cell receptor (TcR) domain. Early and vigorous proliferation of V beta 8+ T-cells precedes their selective deletion, leaving the host unresponsive upon rechallenge with the native immunogen SEB. Nonetheless, this induction of anergy is incompletely understood. Recently we demonstrated that more cells than just V beta 8+ T-cells undergo clonal proliferation after challenge with SEB (Cell. Immunol. 154, 440, 1994). These findings suggested that non-V beta 8+ T-cells may have a role in the induction of superantigen-induced anergy. To further investigate this, we enumerated CD4+ and CD8+ T-cells in lymph nodes and spleens from Balb/c mice at various times after primary and secondary challenge with either a high or a low dose of SEB. Using these kinetic data we investigated whether challenge with SEB would modulate antigen-specific V beta 8-associated T-memory responses. To this end, the V beta 8+ T-cell-associated responses induced by SEB were compared with the V beta 8+ TcR-associated memory responses induced by the nominal antigen sperm whale myoglobin (SWM). Results indicated that challenge of SWM-primed mice with SEB abrogated the V beta 8-associated SWM-specific T-cell memory for an extended but transient period of time. Moreover, prechallenge with SEB blocked the establishment of de novo V beta + T-cell-mediated immunity. These findings suggest that administration of low and controlled doses of microbial superantigen could provide long-term suppression of antigen-specific cell-mediated immunity.