Superantigens augment antigen-specific Th1 responses by inducing IL-12 production in macrophages

Superantigens (SAg) are microbial proteins that mediate antigen-presenting cell (APC)-T cell interaction by cross-linking MHC class II molecules with subsets of TcRVbeta. SAgs are implicated in the pathogenesis of several infectious, inflammatory, and autoimmune diseases. In this study, we examined the influence of SEB on interleukin-12 (IL-12) production and the activation of antigen-specific Th1 responses. Addition of SEB augmented the antigen-induced proliferation of HS-17, a murine MBPp91-103 peptide-specific TcRVbeta6+ CD4+ Th1 clone. SEB augments HS-17 T cell proliferation through its interaction with IA(S) molecules on macrophages, but not with the TcRVbeta6 on HS-17 cells. On binding to IA(S), SEB induces IL-12 production in macrophages, which in turn augments antigen-induced proliferation of HS-17 T cells. Treatment with anti-IA(S) nmAb 10-3.6 inhibited the antigen- and SEB-induced IL-12 production and T cell proliferation. These results suggest that SAgs augment antigen-specific T cell responses by inducing IL-12 production in macrophages.