ACTIVE SUPPRESSION INDUCED BY CUTANEOUS EXPOSURE TO BACTERIAL SUPERANTIGEN IS PREVENTED BY INTERLEUKIN-L2 TREATMENT IN-VIVO

Exposure to the bacterial superantigen staphylococcal enterotoxin B (S EB) leads to inhibition of several immune responses and the induction of regulatory cells. The aim of this study was to characterize these r egulatory cells further and to investigate the effect of interleukin-1 2 (IL-12) on superantigen-induced suppression. For this purpose BALB/c mice were injected subcutaneously with low doses of SEE that did not deplete the SEB-reactive V beta T cells. Intravenous transfer of unsep arated local-draining lymph node cells from these SEE-treated animals suppressed the proliferative response of mononuclear spleen cells of n aive syngeneic recipients for at least 3 weeks, The regulatory cells d id not produce the type 2 cytokines, interleukin-4 (IL-4) or interleuk in-10 (IL-10), or increased amounts of transforming growth factor-beta (TGF-beta). Depletion of CD8(+) or SEB-reactive V beta 7(+) and V bet a 8(+) T cells, prior to transfer, abrogated the suppressive effect. I ntraperitoneal injections of IL-12 into donors, prior to SEB treatment , prevented the induction of functional regulatory cells, and treatmen t of recipients with IL-12, prior to receipt of cells from SEB-treated donors, prevented the suppressive effect of regulatory cells that wer e already induced. The data indicate that exposure to minute amounts o f superantigens directly induces superantigen-reactive and CD8(+) regu latory T cells and that superantigen-induced suppression can be preven ted and reversed by IL-12 treatment in vivo.