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Ann N Y Acad Sci. 2006 Aug;1072:401-6.

Intestinal epithelial antigen induces CD4+ T cells with regulatory phenotype in a transgenic autoimmune mouse model.

Author information

1
Department of Mucosal Immunity, German Research Centre for Biotechnology, Mascheroder Weg 1, D-38124 Braunschweig, Germany. awe@gbf.de

Abstract

Regulatory T cells play a crucial role in the control of immune responses in the intestinal mucosa and their absence may predispose to inflammatory bowel disease (IBD). However, the induction of regulatory T cells at sites of mucosal inflammation is not yet fully understood and may involve antigen presentation by local immature dendritic cells and/or intestinal epithelial cells (IECs). VILLIN-HA mice, which express the hemagglutinin (HA) from influenza virus A exclusively in enterocytes of the intestinal epithelium, were matched with T cell receptor (TCR)-HA mice expressing an alphabeta-TCR which recognizes a major histocompatibility complex (MHC) class II-restricted epitope of HA in order to determine the impact of antigen presentation by IECs on CD4(+) T cell immunity. In VILLIN-HA x TCR-HA mice, peripheral HA-specific lymphocytes showed an activated phenotype and increased infiltration into the intestinal mucosa without destruction of the intestinal epithelium. Mucosal lymphocytes from VILLIN-HA x TCR-HA mice secreted lower amounts of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) and exhibited an increased expression of interleukin-10 (IL-10), Nrp-1, and Foxp3, molecules published as markers for regulatory T cells. IECs can take up and process antigen but the antigen presentation capacity of these cells is often inefficient. Functional and molecular characterization of IECs from VILLIN-HA and VILLIN-HA x TCR-HA transgenic mice revealed a direct role in the induction of CD4(+) T cells with a regulatory phenotype that maintain intestinal homeostasis.

PMID:
17057222
DOI:
10.1196/annals.1326.035
[Indexed for MEDLINE]

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