Intestinal epithelial antigen induces CD4+ T cells with regulatory phenotype in a transgenic autoimmune mouse model.
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.
Westendorf
Astrid M
AM
Department of Mucosal Immunity, German Research Centre for Biotechnology, Mascheroder Weg 1, D-38124 Braunschweig, Germany. awe@gbf.de
Bruder
Dunja
D
Hansen
Wiebke
W
Buer
Jan
J
D000818:Animals; D000941:Antigens / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D018928:Immunity, Mucosal; D009980:Influenza A virus / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic
D000941:Antigens; D000956:Antigens, Viral