Cholera Toxin Suppresses Interleukin (IL)-12 Production and IL-12 Receptor β1 and β2 Chain Expression

摘要: Cholera toxin (CT) is a potent mucosal vaccine adjuvant, which has been shown to induce T helper cell type 2 (Th2) responses in systemic and tissues. We report that CT inhibits the production of interleukin (IL)-12, major Th2 counterregulatory cytokine. IL-12 p70 by stimulated human monocytes was inhibited dose-dependent manner. This suppression occurred at level gene transcription, maximal low concentrations CT, dependent on A subunit toxin, since purified B had minimal effect. also monocyte-derived dendritic cells, as well tumor necrosis factor α, but not IL-10, IL-6, or transforming growth (TGF)-β1, monocytes. The effects were due autocrine TGF-β1, prostaglandin E2. IFN-γ anti-CD3-stimulated peripheral blood mononuclear cell, part production, inhibition expression β1 β2 chains receptor cells. In vivo, mice given before challenge with lipopolysaccharide markedly reduced serum levels p40 interferon γ. These data demonstrate two novel mechanisms can inhibit Th1 immune responses, help explain ability mucosally administered enhance Th2-dependent responses.