Staphylococcal enterotoxin B induces potent cytotoxic activity by intraepithelial lymphocytes

In food poisoning, Staphylococcus aureus secretes staphylococcal enterotoxin B (SEB), a superantigen that causes intense T-cell proliferation and cytotoxicity. The effects of SEB on lytic activity by human intestinal intraepithelial lymphocytes (IEL) were investigated. Jejunal IEL, from morbidly obese individuals undergoing gastric bypass operations, were tested for SEB-induced cytotoxicity against C1R B-lymphoblastoid cells, HT-29 adenocarcinoma cells, or CD1d-transfected cells using the Cr-51-release assay. Fas and Fas ligand expression were detected by immunofluorescence and flow cytometry and soluble ligand by enzyme-linked immunosorbent assay (ELISA). In the presence of SEB, IEL became potently cytotoxic against C1R cells and interferon-gamma (IFN-gamma)-precultured HT-29 cells, causing 55 +/- 10% and 31 +/- 6% lysis, respectively, greater than that by phytohaemagglutinin (PHA)-, interleukin-2 (IL-2)-, or anti-T-cell receptor (TCR)-activated IEL. SEB-stimulated peripheral blood (PB) CD8(+) T cells lysed similar numbers of C1R cells but fewer HT-29 cells (53 +/- 13% and 8 +/- 5%, respectively). IEL killing of C1R cells involved interaction of major histocompatibility complex (MHC) class II with TCR, CD2 with CD58, and CD11a with CD54, and was perforin mediated. SEB-induced IEL lysis of HT-29 cells, in contrast, was caused by an unknown target cell structure, not MHC class II or CD1d, and resulted from a combination of perforin and Fas-mediated events. The potent cytotoxic activities of IEL promoted by SEB utilize two different mechanisms, depending on the surface receptors expressed by the target cells.