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 CD8α α+ 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 CD8α α+ 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 CD8α α+ IEL were reduced following oral feeding with LT. These findings suggest that LT negatively regulates development of CD8α α+ IEL via the disruption of mucosal intranet‐associated cytokine and cytokine receptors, which are required for the development and / or expansion of extrathymically developedT cells. Further, LT‐induced destruction of the mucosal intranet resulted in the impairment of IEC generation via an increase of apoptosis.

Induction of Thymus-Derived γδ T Cells byEscherichia coliEnterotoxin B Subunit in Peritoneal Cavities of Mice

“…The B subunits of these toxins alone are strongly antigenic and appear to have some adjuvant action, but this effect is highly reduced from that seen for the intact holotoxin. Kim et al (15) reported that holo-LT selectively inhibits the extrathymic T-cell development of intestinal epithelial lymphocytes, including ␣␤ and ␥␦ T cells. As yet, however, no reports have demonstrated that CT, LT, or their corresponding B subunits can recruit and activate peritoneal ␥␦ T cells.…”

Proliferation and Differentiation of Hematopoietic Cells and Preservation of Immune Functions

“…Overexpression of MHC class Irelated chain A in the intestine of experimental transgenic mice resulted in a clonal expansion of CD4 + CD8 + IELs and attenuated acute colitis in an experimental model of inflammatory bowel disease induced by dextran sodium sulfate administration (Park et al, 2003). CD8 + IELs developed along an extrathymic pathway may work as antiinflammatory regulator T cells to sustain the mucosal intranet formed by intestinal epithelial cells and IELs and to diminish the expansion of enterotoxigenic Escherichia coli (Kim et al, 2001). Although ingesting SpHW did not significantly increase the level of CD4 + CD8 + IELs in the present study, these facts, in addition to our present results, suggest that ingestion of Spirulina appears to be effective for protecting immune functions or improving immune systems vulnerable to age, thereby reducing the risk of infectious and autoimmune diseases.…”