The protective effect of oral colitis-derived proteins in a murine model of inflammatory bowel disease is associated with an increase in γδ T cells in large intestinal mucosa

Abstract

Oral tolerance has previously been shown effective in preventing several immune-mediated disorders in animal models. The aims of this study were to investigate the effect of oral colitis-extracted proteins (CEP) on dextran sulfate sodium (DSS)-induced colitis in BALB/c mice and to explore the relative role of the intestinal mucosal gammadelta T cells. The effect of five low oral doses of CEP on colitis was evaluated by clinical manifestation and histological lesions. Serum cytokines were measured by enzyme-linked immunosorbent assay. The percentages of the intestinal mucosal gammadelta T cells were evaluated by flow cytometry. CEP-fed colitis mice showed less severe symptoms and histological injury than bovine serum albumin (BSA)-fed control mice. Tolerized mice developed an increase in TGF-beta1 and no change in IFN-gamma serum levels. Increases in TCRgammadelta(+) T cells and CD8alpha(+)TCRgammadelta(+) T cells in small intestinal mucosal lymphocytes and no quantitative change in large intestinal mucosal lymphocytes were demonstrated in colitis mice compared to untreated mice. The proportions of TCRgammadelta(+) T cells and CD8alpha(+)TCRgammadelta(+) T cells in large intestinal mucosal lymphocytes from CEP-fed colitis mice were significantly higher compared to BSA-fed controls. The disease activity index negatively correlated with the percentages of large intestinal mucosal gammadelta T cells. Furthermore, mucosal repair in repair-period mice was also accompanied by increases in TCRgammadelta(+) T cells and CD8alpha(+)TCRgammadelta(+) T cells in large intestinal mucosal lymphocytes. Improvement of DSS-induced colitis that resulted from oral administration of colitis-extracted proteins is associated with an increase in gammadelta T cells in large intestinal mucosa.