Orally administered cholera toxin prevents murine intestinal T cells from staphylococcal enterotoxin B-induced anergy

Abstract

Background & Aims: Cholera toxin (CT) has been shown to be a strong mucosal adjuvant for the induction of antigen-specific secretory immunoglobulin A (IgA). The mechanism of adjuvant activity of CT is still unknown. The aim of this study was to examine the immunomodulatory function of CT on mucosal T cells using staphylococcal enterotoxin B (SEB) as coadministered oral antigen, because SEB has been shown to directly regulate αβ T-cell responses. Methods: C3H/HeN mice were orally or systemically immunized with SEB and/or CT. The levels of SEB-specific antibodies and frequencies of CD4 +Vβ8 + T cells were analyzed. SEB-specific T-cell proliferation and cytokine production were also determined. Results: Neither SEB-specific IgA nor IgG antibodies were induced in feces when SEB was administered alone. This was a result of the clonal deletion and partial unresponsiveness of CD4 +Vβ8 +T cells in Peyer's patches. On the other hand, SEB-specific antibodies were induced by oral immunization with SEB and CT. Although some degree of clonal deletion was induced by oral immunization with SEB and CT, coadministered CT prevented the induction of anergy for CD4 +Vβ8 + T cells in Peyer's patches. Conclusions: CT is a powerful immunomodulatory molecule that prevents mucosal T cells from SEB-induced anergy. GASTROENTEROLOGY 1998;115:1197-1204