title: CD4+ intestinal mucosal lymphocytes in the pathogenesis of Crohn's disease.
abstract: To analyze the nature of intestinal mucosal lymphocytes in Crohn's disease, we established T cell lines of patients' intraepithelial lymphocytes. T cell lines from the affected terminal ileum of the patients showed an increased proportion of CD4+V beta 5.2/5.3+ T cells. These cells were increased in number after stimulation with staphylococcal enterotoxins C1 and D, showed an increase in cytolytic activity, and produced a large amount of interferon-gamma. To clarify the role of CD4+ mucosal lymphocytes in the intestinal inflammation, we then developed a novel colitis model by immunizing a rat with trinitrobenzenesulfonic acid (TNB) emulsion with adjuvant. Deep ulceration and granuloma formation in this colitis model resembled the histopathological findings of human Crohn's disease. Immunohistochemical and flow cytometric analysis demonstrated that the number of CD45RC(high)CD4+ mucosal lymphocytes was increased. Interestingly, the administration of anti-CD4 Abs prevented severe inflammation in the model. After treatment with anti-CD4 Abs, the anti-TNB Ab titer, the number of CD45RC(high)CD4+ cells, and interferon-gamma mRNA expression were significantly decreased in the mucosa of the model. These results suggest that some subsets of CD4+ mucosal lymphocytes play an important role in the triggering and progression of inflammation in Crohn's disease.
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
authors.forename: H
authors.initials: H
authors.lastname: Takaishi
authors.forename: Y
authors.initials: Y
authors.lastname: Hosoda
authors.forename: T
authors.initials: T
authors.lastname: Ezaki
authors.forename: T
authors.initials: T
authors.lastname: Yajima
authors.forename: N
authors.initials: N
authors.lastname: Inoue
authors.forename: Y
authors.initials: Y
authors.lastname: Ueno
authors.forename: Y
authors.initials: Y
authors.lastname: Iwao
authors.forename: H
authors.initials: H
authors.lastname: Ishii
authors.forename: H
authors.initials: H
authors.lastname: Ishikawa
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003092:Colitis / Q000276:immunology; D003106:Colon / Q000276:immunology / Q000473:pathology; D003424:Crohn Disease / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007082:Ileum / Q000276:immunology / Q000473:pathology; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar