CD4+ T cells mediate superantigen-induced abnormalities in murine jejunal ion transport

The immunomodulatory properties of bacterial superantigens (SAgs) have been defined, yet comparatively little is known of how SAgs may affect enteric physiology. Staphylococcus aureus enterotoxin B (SEB) was used to examine the ability of SAgs to alter epithelial ion transport. BALB/c mice, severe combined immunodeficient (SCID, lack T cells) mice, or SCID mice reconstituted with lymphocytes or CD4(+) T cells received SEB intraperitoneally, and jejunal segments were examined in Ussing chambers; controls received saline only. Baseline short-circuit current (I-sc, indicates net ion transport) and I-sc responses evoked by electrical nerve stimulation, histamine, carbachol, or forskolin were recorded. Serum levels of interleukin-fl (IL-2) and interferon-gamma (IFN-gamma) were measured. SEB-treated BALB/c mice showed elevated serum IL-2 and IFN-gamma levels, and jejunal segments displayed a time-and dose-dependent increase in baseline I-sc compared with controls. Conversely, evoked ion secretion was selectively reduced in jejunum from SEB-treated mice. Elevated cytokine levels and changes in jejunal I-sc were not observed in SEB-treated SCID mice. In contrast, SCID mice reconstituted with T cells were responsive to SEB challenge as shown by increased cytokine production and altered jejunal I-sc responses that were similar to those observed in jejunum from SEB-treated BALB/c mice. We conclude that exposure to a model bacterial SAg causes distinct changes in epithelial physiology and that these events can be mediated by CD4(+) T cells.