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 TcRV beta, SAgs are implicated in the pathogenesis of several infectious, inflammatory, and autoimmune diseases. In this study, rue examined the influence of SEE on interleukin-12 (IL-12) production and the activation of antigen-specific Till responses. Addition of SEE augmented the antigen-induced proliferation of HS-17, a murine MBPp91-103 peptide-specific TcRV beta 6(+) CD4(+) Th1 clone. SEE augments HS-17 T cell proliferation through its interaction with IA(s) molecules on macrophages, hot not with the TcRV beta 6 on HS-17 cells. On binding to IAS, SEE induces IL-12 production in macrophages, which in turn augments antigen-induced proliferation of HS-17 T cells. Treatment with anti-IA(s) mAb 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.