Induction of a Cytokine Network by Superantigens with Parallel TH1 and TH2 Stimulation

Abstract

Superantigens cross-link the MHC class II molecule on accessory cells with the V beta region of the TCR outside the antigen binding sites. In this study, we compared the capacity of the staphylococcal entertoxins (SE) A, B, C1, C2, C3, D, and E, the toxic shock syndrome toxin (TSST) 1, the exfoliative toxin (ExFT) A, and the Streptococcus pyogenes erythrogenic exotoxins (SPE) B and C to induce cytokine release in human peripheral blood mononuclear cells. We showed that all toxins tested induced IL-1 alpha and beta, IL-2, IL-4, IL-6, IFN-gamma, and TNF-alpha, but not IFN-alpha. However, we found that SPEB differed from all other toxins tested, because its cytokine induction was significantly lower than that of the other toxins. This was not true of IL-6 and IL-10 induction, in which SPEB showed similar amounts of IL-6 compared with all other toxins and of IL-10 in comparison to SEC2. SPEB showed a specificity for TH2 cells, whereas the other toxins stimulated TH1 as well as TH2 cells very strongly. As a result, superantigens appear to be able to uncouple the TH1/TH2 antagonism. Collectively, our results indicate that SPEB seems not to be a superantigen or represents a different group of microbial superantigens. Furthermore, superantigens stimulate TH1 as well as TH2 cells without any preference and therefore they are able to induce humoral as well as cellular immunity. This could be one reason for the existence of autoantibodies and autoreactive T cells in autoimmune diseases and one major step in the beginning of the induction of autoreactivity.