The effect of oral tolerance on the roles of small intestinal intraepithelial lymphocytes in murine colitis induced by dextran sodium sulfate

Abstract

There is increasing evidence that gut-derived intraepithelial lymphocytes have potent cytolytic and immunoregulatory functions, which they use to sustain epithelial integrity. The aims of this study were to investigate the roles of small intestinal intraepithelial lymphocytes (SI-IELs) in oral tolerance and dextran sodium sulfate (DSS)-induced colitis. SI-IELs or sorted γδ T cells from untreated, colitis, and colitis-extracted protein (CEP)-fed colitis mice were adoptively transferred to BALB/c mice; colitis was then induced with DSS. Cytokines were analyzed in sera from mice and culture supernatants. Transfer of SI-IELs or sorted γδ T cells from untreated and colitis mice all alleviated experimental colitis. Mice orally administered with five low doses of CEP showed less severe symptoms and histological injury. SI-IELs from CEP-fed colitis mice more significantly ameliorated colitis than those from control mice (weight, 94.1 ± 2.5% vs. 89.8 ± 2.6%, p < 0.05; disease activity index, 7.2 ± 1.2 vs. 8.7 ± 1.9, p < 0.05; histological scores, 22.1 ± 2.8 vs. 25.7 ± 2.1, p < 0.05, n = 8 per group); however, not did SI-γδ IELs from CEP-fed colitis mice. Alleviation of colitis was accompanied by an increase of TGF-β1 secretion and no change of IFN-γ in sera and culture supernatants. The level of serum TGF-β1 was negatively related to the severity of colitis. The protective effects of SI-IELs in DSS-induced colitis were partly accomplished by γδ T cells and could be mediated by TGF-β but were not associated with IFN-γ. Oral tolerance strengthens the suppressive effects of regulatory subsets in SI-IELs.