Staphylococcal enterotoxin B induces potent cytotoxic activity by intraepithelial lymphocytes

In food poisoning, Staphylococcus aureus secretes staphylococcal enterotoxi n B (SEB), a superantigen that causes intense T-cell proliferation and cyto toxicity. The effects of SEB on lytic activity by human intestinal intraepi thelial lymphocytes (IEL) were investigated. Jejunal IEL, from morbidly obe se individuals undergoing gastric bypass operations, were tested for SEB-in duced cytotoxicity against C1R B-lymphoblastoid cells, HT-29 adenocarcinoma cells, or CD1d-transfected cells using the Cr-51-release assay. Fas and Fa s ligand expression were detected by immunofluorescence and flow cytometry and soluble ligand by enzyme-linked immunosorbent assay (ELISA). In the pre sence of SEB, IEL became potently cytotoxic against C1R cells and interfero n-gamma (IFN-gamma)-precultured HT-29 cells, causing 55 +/- 10% and 31 +/- 6% lysis, respectively, greater than that by phytohaemagglutinin (PHA)-, in terleukin-2 (IL-2)-, or anti-T-cell receptor (TCR)-activated IEL. SEB-stimu lated peripheral blood (PB) CD8(+) T cells lysed similar numbers of C1R cel ls but fewer HT-29 cells (53 +/- 13% and 8 +/- 5%, respectively). IEL killi ng of C1R cells involved interaction of major histocompatibility complex (M HC) 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 f rom a combination of perforin and Fas-mediated events. The potent cytotoxic activities of IEL promoted by SEB utilize two different mechanisms, depend ing on the surface receptors expressed by the target cells.