Background Atopic dermatitis (AD) is a chronic skin disease associated with increased IgE synthesis and colonization with Staphyiococcus aureus secreting exotoxins, such as Toxic Shock Syndrome Toxin-1 (TSST-1).
Objectives In this study, we were interested in determining the in vitro effects of TSST-1 on IgE synthesis in peripheral blood mononuclear cells from patients with AD.
Methods We stimulated peripheral blood mononuclear cells (PBMC) from AD patients with a wide range of TSST-1 concentrations and measured IgE synthesis by enzyme-linked immunosorbent assay (ELISA) after 14 days.
Results We show herein that TSST-1 produced antagonistic effects on IgE synthesis by PBMC from AD patients, depending on the concentration used: IgE synthesis was inhibited at 1000 pg/mL (P<0.05) and enhanced at 0.01 pg/mL (P<0.01) of toxin. TSST-1 was found to induce the production of much higher amounts of interferon-gamma (IFNγ) at 1000 pg/mL than at 0.01pg/mL of toxin (P= 0.0001). More importantly, immunoglobulin E (IgE) synthesis was enhanced by TSST-1 at 1 pg/mL in the presence of antibodies blocking IFN-γ activity. The other immunoglobulin (Ig) isotypes were also increased after TSST-1 stimulation suggesting that the enhanced IgE synthesis was secondary to a polyclonal B cell activation rather than an isotype switch. TSST-1-stimulated IgE synthesis was T cell-dependent because purified tonsil B cells were only able to synthesize increased amounts of IgE when small numbers of T cells were added to the cultures. Anti-HLA-DR and anti-LFA-1 monoclonal antibodies (MoAb) inhibited TSST-1-enhanced IgE synthesis, suggesting that the bridging of the T cell receptor (TCR) and major histocompalibilily complex (MHC) class II on B cells was necessary for activation of B cell differentiation.
Conclusion These data indicate that staphylococcal superantigens are able, at concentrations inducing low amounts of IFNγ, to stimulate IgE synthesis by PBMC from AD patients, and suggest that staphylococcal toxins may contribute to elevated IgE synthesis in AD.