Active suppression induced by cutaneous exposure to bacterial superantigen is prevented by interleukin-12 treatment in vivo.

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