Inhibition of T-cell response by Escherichia coli heat-labile enterotoxin-treated epithelial cells

Escherichia coli heat-labile enterotoxin (LT) is an extensively studied adj uvant of mucosal responses. Nevertheless, its mode of action as an adjuvant remains incompletely understood. In this study, we describe a simplified i n vitro model with which to look at some aspects of immunoregulation by LT. The interaction of LT with the apical surface of a monolayer of CaCo-2 epi thelial cells induces the release of a soluble factor which inhibits the an tigen-induced release of interleukin-2 by T cells cultured at the basolater al side of the cells. The release of this factor requires the ADP-ribosylat ing activity of LT since the isolated B subunit, as well as an enzymaticall y silent LT mutant, loses biological activity in this model. The inhibitory activity is likely to be due to prostaglandin release, since it is blocked by indomethacin. The contribution of LT-induced prostaglandin release to t he complex immunoregulatory activity of LT is discussed.