The superantigen toxic shock syndrome toxin-1 induces CD40 ligand expression and modulates IgE isotype switching.
Isotype switching to IgE requires two signals. The first signal is provided by the cytokines IL-4 or IL-13, and the second signal is delivered by the interaction between the B cell antigen CD40 and its ligand (CD40L) which is expressed on activated T cells. Since superantigens have been shown to activate T cells, we examined the effect of the superantigen toxic shock syndrome toxin-1 (TSST-1) on CD40L expression on T cells. TSST-1 induced expression of CD40L in both freshly isolated T cells and in T cell lines expanded by re-stimulation with TSST-1. CD40L was preferentially expressed in the V beta 2 subset of T cells expanded by TSST-1. We next examined the effect of TSST-1 on IgE synthesis by human peripheral blood mononuclear cells (PBMC). Addition of TSST-1 to PBMC inhibited IL-4-induced IgE synthesis in a dose-dependent manner. This inhibition was reversed partly by adding a neutralizing antibody to IFN-gamma. In contrast, TSST-1 induced high amounts of IgE synthesis in the presence of IL-4 at low T:B cell ratios (0.5:10 to 4:10), a condition which circumvents the inhibitory effect of IFN-gamma. TSST-1 induction of IgE synthesis was inhibited by a mAb to CD40L. These results indicate that superantigens induce CD40L expression in T cells and cause isotype switching in B cells which is mediated by CD40L-CD40 interaction.
Jabara
H H
HH
Division of Immunology, Children's Hospital, Boston, MA, USA.
Geha
R S
RS
D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D001427:Bacterial Toxins; D023201:CD40 Ligand; D004768:Enterotoxins / Q000494:pharmacology*; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000187:drug effects*; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology*; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000187:drug effects; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D001427:Bacterial Toxins; D004768:Enterotoxins; D008024:Ligands; D008562:Membrane Glycoproteins; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; D023201:CD40 Ligand; D007073:Immunoglobulin E