title: Changes in the rate of crypt epithelial cell proliferation and mucosal morphology induced by a T-cell-mediated response in human small intestine.
abstract: The rate of crypt epithelial cell proliferation and mucosal morphology have been studied in vitro in explants of fetal human small intestine in organ culture in which a cell-mediated immune response has been elicited by stimulating lamina propria T cells with pokeweed mitogen or monoclonal anti-CD3 antibodies. Twelve hours after the addition of anti-CD3 or pokeweed mitogen, most lamina propria T cells expressed CD25. By 18 and 24 h after the addition of anti-CD3, there were significantly more crypt cells in the cell cycle than in controls, although villus height and crypt depth are the same in both groups. After 3 days, by dissecting microscopy, the villi appeared shorter in cultures in which the T cells were stimulated than in control cultures, and the mucosal surface was obscured by a layer of extruded enterocytes. Villus atrophy was confirmed by direct measurement of Feulgen-stained, microdissected villi. Crypts were longer in T-cell-stimulated cultures, and the rate of crypt epithelial cell proliferation measured by metaphase arrest was increased 10-fold. By electron microscopy, the microvilli and cellular morphology of the surface enterocytes were normal in T-cell-stimulated cultures. These experiments clearly show that a profound immune-mediated crypt epithelial cell hyperplasia can occur in the absence of damage to surface enterocytes.
authors: Department of Paediatric Gastroenterology, St. Bartholomews Hospital, London, England.
authors: R C
authors: RC
authors: Ferreira
authors: L E
authors: LE
authors: Forsyth
authors: P I
authors: PI
authors: Richman
authors: C
authors: C
authors: Wells
authors: J
authors: J
authors: Spencer
authors: T T
authors: TT
authors: MacDonald
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001284:Atrophy / Q000473:pathology; D017252:CD3 Complex; D002455:Cell Division; D004848:Epithelium / Q000648:ultrastructure; D005333:Fetus; D005455:Fluorescent Antibody Technique; D006801:Humans; D006984:Hypertrophy / Q000473:pathology; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000648:ultrastructure*; D007421:Intestine, Small / Q000648:ultrastructure*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008854:Microscopy, Electron; D008871:Microvilli / Q000648:ultrastructure; D009924:Organ Culture Techniques; D011043:Pokeweed Mitogens / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D011043:Pokeweed Mitogens; D011948:Receptors, Antigen, T-Cell