Influence of enterotoxin on mucosal intranet: Selective inhibition of extrathymic T cell development in intestinal intraepithelial lymphocytes by oral exposure to heat-labile toxin

Abstract

We tested the possibility that heat-labile enterotoxin of Escherichia coli (LT) affects the development of extrathymic T cells in the intraepithelial lymphocyte (IEL) compartment. After oral administration of LT, the number of extrathymic CD8αα+ IEL was selectively and significantly diminished when compared with the corresponding cells in phosphate-buffered saline-fed control mice. To clarify the mechanism behind this selective reduction of CD8αα+ IEL, we analyzed the expression of essential cytokines and their corresponding receptors for the mucosal intranet formed by intestinal epithelial cells (IEC) and IEL. The expression levels of stem cell factor, interleukin (IL)-7, and IL-15 in IEC, and their corresponding receptors, i.e. c-kit, IL-7 receptor, and IL-15 receptor, in CD8αα+ IEL were reduced following oral feeding with LT. These findings suggest that LT negatively regulates development of CD8αα+ IEL via the disruption of mucosal intranet-associated cytokine and cytokine receptors, which are required for the development and/or expansion of extrathymically developed T cells. Further, LT-induced destruction of the mucosal intranet resulted in the impairment of IEC generation via an increase of apoptosis.