Superantigen-induced T cell death by apoptosis: analysis on a single cell level and effect of IFN-gamma and IL-4 treatment

BACKGROUND: A role of bacterial superantigens in several chronic inflammatory diseases has previously been proposed. Many of these diseases are associated with an imbalance of the T helper cell subsets and their cytokine production. METHODS: Peripheral blood mononuclear cells from healthy donors were incubated with various concentrations of staphylococcal enterotoxin B (SEB) with or without IL-4 or IFN-gamma. After different time points cell activation, proliferation, Fas expression, cytokine release and cell death via apoptosis were detected. RESULTS: SEB treatment resulted in sequential T cell activation, proliferation, Fas expression, cytokine release, subsequently followed by cell death via apoptosis in a dose- and time-dependent manner. This biphasic effect occurred preferentially in SEB-responsive cells represented by the expression of Vbeta3 and Vbeta12 on T cells. A strong relationship between T cell activation and apoptosis was observed. The amplitude between these events increased with the dose of SEB. The highest rate of apoptotic T cells was observed at a dose of 1,000 ng/ml SEB. Addition of IFN-gamma to SEB-treated cells significantly reduced the rate of apoptotic cells, whereas IL-4 prevented apoptosis only in SEB-untreated cells. CONCLUSION: These results support the concept that the dose of superantigen exposure determines the rate of T cell proliferation and subsequent cell death. This T cell immune response is modulated by the presence and the type of cytokines.