title: Intestinal epithelial cells from inflammatory bowel disease patients preferentially stimulate CD4+ T cells to proliferate and secrete interferon-gamma.
abstract: Previous studies have suggested that intestinal epithelial cells (IECs) have the capacity to function as nonprofessional antigen presenting cells that in the normal state preferentially activate CD8+ T cells. However, under pathological conditions, such as those found in inflammatory bowel disease (IBD), persistent activation of CD4+ T cells is seen. The aim of this study was to determine whether the IBD IECs contribute to CD4+ T cell activation. Freshly isolated human IECs were obtained from surgical specimens of patients with or without IBD and cocultured with autologous or allogeneic peripheral blood T lymphocytes. Cocultures of normal T cells and IECs derived from IBD patients resulted in the preferential activation of CD4+ T cell proliferation that was associated with significant IFN-gamma, but not IL-2, secretion. Cytokine secretion and CD4+ T cell proliferation was inhibited by pretreatment of the IBD IECs with the anti-DR MAb L243. In contrast, normal IECs stimulated the proliferation and cytokine secretion by CD4+ T cells to a significantly lesser degree than IBD IECs. Furthermore, blockade of human leukocyte antigen-DR had a lesser effect in the normal IEC-CD4+ T cell cocultures. We conclude that IECs can contribute to the ongoing CD4+ T cell activation seen in IBD. We suggest that the apparent differences between the secreted levels of IFN-gamma indicate that it may play a dual role in intestinal homeostasis, in which low levels contribute to physiological inflammation whereas higher levels are associated with an uncontrolled inflammatory state.
authors.affiliation: IBD Service, Dept. of Gastroenterology and Liver Diseases, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel. irisd@tasmc.health.gov.il
authors.forename: Iris
authors.initials: I
authors.lastname: Dotan
authors.forename: Matthieu
authors.initials: M
authors.lastname: Allez
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakazawa
authors.forename: Jens
authors.initials: J
authors.lastname: Brimnes
authors.forename: Micoll
authors.initials: M
authors.lastname: Schulder-Katz
authors.forename: Lloyd
authors.initials: L
authors.lastname: Mayer
mesh_terms: D000911:Antibodies, Monoclonal; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002450:Cell Communication; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003093:Colitis, Ulcerative / Q000276:immunology / Q000378:metabolism; D003424:Crohn Disease / Q000276:immunology / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology* / Q000473:pathology; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007371:Interferon-gamma / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation
chemical_list: D000911:Antibodies, Monoclonal; D006684:HLA-DR Antigens; C508609:IL10 protein, human; D007376:Interleukin-2; D016753:Interleukin-10; D007371:Interferon-gamma