Cholera Toxin Enhances Alloantigen Presentation by Cultured Intestinal Epithelial Cells

Abstract

In the present study we show that cholera toxin (CT) strongly potentiates antigen presentation by intestinal epithelial cells, probably by enhancing co-stimulation. This was demonstrated in an allogeneic system using cells from the IEC-17 rat epithelial cell line as antigen presenting cells (APC). These cells were induced by optimal concentrations of IFN-gamma to express good amounts of Ia antigen and cultured for 24-48 h in the presence or absence of CT. Thereafter the cells were thoroughly washed and added to cultures containing MHC-incompatible spleen cells as responder cells. Epithelial cells exposed to CT demonstrated greatly enhanced ability to trigger allogen-specific T-cell proliferation as compared with IEC-17 cells treated with IFN-gamma alone. The mechanism for the enhanced APC function was investigated by analysing CT-treated IEC-17 cells for increased class II MHC antigen expression or enhanced production of cytokines with known co-stimulatory function. We found no significant increase in class II MHC antigen expression. By contrast, CT strongly promoted, in a dose-dependent fashion, the production of both IL-1 and IL-6 cytokines by IEC-17 cells as compared with untreated epithelial cells. This effect of CT was specific and not due to contaminating endotoxin because excess amounts of soluble toxin receptor, ganglioside GM1, added to the IEC-17 cultures completely abrogated the cytokine response to CT. These results together with our previous findings of enhanced antigen presentation by macrophages stimulated by CT suggest that the potent adjuvant function of CT for induction of mucosal immune responses might be attributed to an enhanced co-stimulating ability of several putative APC in the mucosal immune system: macrophages, B cells and epithelial cells.