SUPERANTIGEN ACTIVATION OF IMMUNE CELLS EVOKES EPITHELIAL (T84) TRANSPORT AND BARRIER ABNORMALITIES VIA IFN-GAMMA AND TNF-ALPHA - INHIBITION OF INCREASED PERMEABILITY, BUT NOT DIMINISHED SECRETORY RESPONSES BYTGF-BETA(2)

Superantigens (SAgs) are extremely potent stimulants of T cell activit y that have been implicated in the etiopathophysiology of inflammatory disease, Here, we tested the hypothesis that Staphylococcus aureus en terotoxin B (SEE), a model SAg, can alter epithelial transport and/or barrier functions via immune stimulation, Confluent monolayers of the human colonic T84 epithelial cell line, grown on filter supports, were cocultured with SEE +/- PBMC. Subsequently, T84 transport (consisting of baseline short-circuit current (Isc, indicates net ion transport) and secretory responses to carbachol and forskolin) and barrier functi ons (consisting of transepithelial resistance and fluxes of H-3-labele d mannitol and Cr-51-EDTA) were examined in Ussing chambers, T84 monol ayers cocultured with SEE-activated PBMC displayed a time-and dose-dep endent decrease in secretory responses to carbachol and forskolin and a significant increase in permeability, These dramatic changes in epit helial function were not due to reduced epithelial viability, Neutrali zing Abs to IFN-gamma partially prevented the transport abnormalities, and Abs to TNF-alpha inhibited the increase in epithelial permeabilit y, Abs to IL-1 beta and IL-6 did not modulate the SEE-activated PBMC-i nduced T84 pathophysiology, Addition of TGF-beta(2) to conditioned med ium from SEB-activated PBMC partially inhibited the increase in T84 pe rmeability but did not affect the transport abnormalities, We conclude that SAgs can elicit epithelial irregularities characteristic of ente ric inflammation and that IFN-gamma and TNF-alpha are key mediators in this coculture model of epithelial dysfunction, Additionally, we woul d highlight the role that TGF-beta(2) may play in preventing prolonged increases in epithelial permeability.