title: Spontaneous chronic colitis in TCR alpha-mutant mice; an experimental model of human ulcerative colitis.
abstract: Mice with targeted disruption of the T cell receptor alpha gene (TCR alpha-/-) spontaneously develop chronic colitis. Colonic inflammation begins at 6-8 weeks of age and chronic colitis is established in about 60% of mice by 16-20 weeks of age. The disease is also associated with autoantibodies (anti-tropomyosin antibodies, anti-neutrophil cytoplasmic antibodies) and an oligoclonal immune response to luminal bacterial antigens. Although T cells, but not B cells or autoantibodies, are essential for the development of colitis, B cells and/or autoantibodies may have a regulatory role in the pathogenesis of this colitis because the colitis is more severe in B cell deficient TCR alpha-/- mice. Cytokines, specifically IL-4 and IL-1, also play an important role in the development of colitis in TCR alpha-/- mice. Enteric bacteria located in the large intestine are an important factor in the pathogenesis of this colitis because germ-free TCR alpha-/- mice do not develop colitis and appendectomy at an early age delays the onset of this colitis. The colitis in TCR alpha-/- mice resembles human ulcerative colitis and provides a useful model to study the pathogenesis of human inflammatory bowel disease.
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston 02114, USA. abhan@partners.org
authors.forename: A K
authors.initials: AK
authors.lastname: Bhan
authors.forename: E
authors.initials: E
authors.lastname: Mizoguchi
authors.forename: R N
authors.initials: RN
authors.lastname: Smith
authors.forename: A
authors.initials: A
authors.lastname: Mizoguchi
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D003093:Colitis, Ulcerative / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta