Premium
Intestinal Epithelial Antigen Induces CD4 + T Cells with Regulatory Phenotype in a Transgenic Autoimmune Mouse Model
Author(s) -
WESTENDORF ASTRID M.,
BRUDER DUNJA,
HANSEN WIEBKE,
BUER JAN
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1326.035
Subject(s) - villin , biology , foxp3 , intestinal epithelium , mhc class ii , antigen presentation , antigen , immune system , major histocompatibility complex , t cell , immunology , t cell receptor , intestinal mucosa , antigen presenting cell , microbiology and biotechnology , epithelium , medicine , actin , genetics
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 αβ‐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 × 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 × TCR‐HA mice secreted lower amounts of interferon‐γ (IFN‐γ) 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 × TCR‐HA transgenic mice revealed a direct role in the induction of CD4 + T cells with a regulatory phenotype that maintain intestinal homeostasis.