In vivo staphylococcal enterotoxin B (SEB)-primed murine splenocytes secrete mediators which suppress CD25(hi) expression and cell cycle progression of naive splenocytes in response to SEB in vitro

Administration of bacterial superantigen results in clonal activation of T cells followed by a state of hyporesponsiveness to subsequent antigen stimu lation. Using a coculture system, we showed that the splenocytes from staph ylococcal enterotoxin B (SEB)-injected BALB/c mice suppressed the prolifera tive response of naive splenocytes to SEB stimulation. The suppressive effe ct also occurred in Fas-deficient MRL-lpr/lpr mice. When naive responder ce lls were separated by a semipermeable membrane from SEB-primed effector cel ls, the suppressive effect remained apparent. The hyporesponsiveness of res ponder cells did not result from excessive induction of apoptosis, but rath er from prevention of entering the S and G2/M phases of the cell cycle. The IL-2 levels in culture supernatants were low with the presence of SEB-prim ed effector cells. However, addition of IL-2 to the cocultures only partial ly reversed the inhibitory effect. Further studies revealed a reduced level of the CD25(hi) subpopulation in responder cells when cultured in the tran swell with the presence of SEB-primed effector cells compared to that with saline-primed controls. This inhibitory effect was not observed for SEB-ind uced activation of CD25(int) and CD69 expression. Taken together, using a t ranswell culture system, we show in this study an inhibition of CD25(hi) ex pression and cell cycle arrest in target cells, which may serve at least in part the mechanisms of SEB-induced hyporesponsiveness. (C) 2000 Academic P ress.