THE MUCOSAL ADJUVANTICITY OF CHOLERA-TOXIN INVOLVES ENHANCEMENT OF COSTIMULATORY ACTIVITY BY SELECTIVE UP-REGULATION OF B7.2 EXPRESSION

Cholera toxin (CT) is a potent mucosal immunogen and adjuvant that can strongly prime mucosal T cells, The present study was undertaken to i nvestigate the effects of CT on the expression and functional activity of the costimulatory molecules B7.1 and B7.2 on macrophages and the r elationship of these effects to the mucosal adjuvanticity of CT, Bone marrow macrophages (BMM) were generated by culturing bone marrow with macrophage CSF or granulocyte-macrophage CSF. After treatment with eit her CT alone or IFN-gamma alone, B7.2 expression on BMM was moderately up-regulated and was further increased when BMM were treated with bot h CT and IFN-gamma together, Interestingly, CT had no effect on B7.1 e xpression despite the close relationship between these two molecules, Up-regulation of B7.2 expression by CT was mediated by intracellular c AMP production, in that CT-B subunit had no effect and dibutyryl cAMP could mimic the effect, CT increased functional costimulatory activity of macrophages for both anti-CD3-stimulated and allostimulated T cell s, an increase that was blocked by anti-B7.2, but not anti-B7.1, Ab, B 7.2 expression by Mac1(+) Peyer's patch cells was increased after intr aluminal exposure to CT in vivo. Treatment of mice with anti-B7.2 Ab i n vivo inhibited both the mucosal adjuvanticity and the immunogenicity of CT. We conclude that CT enhances the costimulatory activity of muc osal APC by differentially up-regulating B7.2 expression, an effect th at appears to be important for its mucosal adjuvanticity and immunogen icity.