title: Expression of nonclassical class I molecules by intestinal epithelial cells.
abstract: It is well recognized that the nature of the immune response is different in the intestinal tract than in peripheral lymphoid organs. The immunologic tone of the gut-associated lymphoid tissue is one of suppression rather than active immunity, distinguishing pathogens from normal flora. Failure to control mucosal immune responses may lead to inflammatory diseases such as Crohn's disease (CD) and ulcerative colitis (UC) and celiac disease. It has been suggested that this normally immunosuppressed state may relate to unique antigen-presenting cells and unique T-cell populations. The intestinal epithelial cell (IEC) has been proposed to act as a nonprofessional antigen-presenting cell (APC). Previous studies have suggested that antigens presented by IECs result in the activation a CD8(+) regulatory T-cell subset in a nonclassical MHC I molecule restricted manner. We therefore analyzed the expression of nonclassical MHC I molecules by normal IECs and compared this to those expressed by inflammatory bowel disease (IBD) IECs. Normal surface IEC from the colon and, to a much lesser extent, the small bowel express nonclassical MHC I molecules on their surface. In contrast, mRNA is expressed in all intestinal epithelial cells. Surface IEC express CD1d, MICA/B, and HLA-E protein. In contrast, crypt IECs express less or no nonclassical MHC I molecules but do express mRNA for these molecules. Furthermore, the regulation of expression of distinct nonclassical class I molecules is different depending on the molecule analyzed. Interestingly, IECs derived from patients with UC fail to express any nonclassical MHC I molecules (protein and HLA-E mRNA). IECs from CD patients express HLA-E and MICA/B comparable to that seen in normal controls but fail to express CD1d. Thus, in UC there may be a failure to activate any nonclassical MHC I molecule restricted regulatory T cells that may result in unopposed active inflammatory responses. In CD only the CD1d-regulated T cells would be affected.
authors.affiliation: Immunobiology Center, Mount Sinai Medical Center, New York, New York 10029, USA.
authors.forename: Lilani
authors.initials: L
authors.lastname: Perera
authors.forename: Ling
authors.initials: L
authors.lastname: Shao
authors.forename: Anjlee
authors.initials: A
authors.lastname: Patel
authors.forename: Kelly
authors.initials: K
authors.lastname: Evans
authors.forename: Bertrand
authors.initials: B
authors.lastname: Meresse
authors.forename: Richard
authors.initials: R
authors.lastname: Blumberg
authors.forename: Daniel
authors.initials: D
authors.lastname: Geraghty
authors.forename: Veronika
authors.initials: V
authors.lastname: Groh
authors.forename: Thomas
authors.initials: T
authors.lastname: Spies
authors.forename: Bana
authors.initials: B
authors.lastname: Jabri
authors.forename: Lloyd
authors.initials: L
authors.lastname: Mayer
mesh_terms: D018949:Antigens, CD1 / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000276:immunology*; D003424:Crohn Disease / Q000276:immunology*; D005786:Gene Expression Regulation; D006680:HLA Antigens / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D000097625:HLA-E Antigens
chemical_list: D018949:Antigens, CD1; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma; D012333:RNA, Messenger; D000097625:HLA-E Antigens; C099187:MHC class I-related chain A