The superantigen toxic shock syndrome toxin-1 induces CD40 ligand expression and modulates lgE isotype switching

Isotype switching to IgE requires two signals. The first signalis provided by the cytokines IL-4 or IL-13, and the second signalis delivered by the interaction between the B cell antigen CD40and its ligand (CD40L) which is expressed on activated T cells.Since superantigens have been shown to activate T cells, weexamined the effect of the superantigen toxic shock syndrometoxin-1 (TSST-1) on CD40L expression on T cells. TSST-1 inducedexpression of CD40L in both freshly isolated T cells and inT cell lines expanded by re-stimulation with TSST-1. CD40L waspreferentially expressed in the V_ß2 subset of T cellsexpanded by TSST-1. We next examined the effect of TSST-1 onIgE synthesis by human peripheral blood mononuclear cells (PBMC).Addition of TSST-1 to PBMC inhibited IL-4-induced IgE synthesisin a dose-dependent manner. This inhibition was reversed partlyby adding a neutralizing antibody to IFN-. In contrast, TSST-1induced high amounts of IgE synthesis in the presence of IL-4at low T: B cell ratios (0.5: 10 to 4: 10), a condition whichcircumvents the inhibitory effect of IFN-. TSST-1 inductionof IgE synthesis was inhibited by a mAb to CD40L. These resultsindicate that superantigens induce CD40L expression in T cellsand cause isotype switching in B cells which is mediated byCD40L-CD40 interaction.