Spontaneous development of inflammatory bowel disease in T cell receptor mutant mice.
We describe the spontaneous development of inflammatory bowel disease (IBD) in several immunodeficient mouse strains created via gene targeting in embryonic stem cells. Chronic colitis was observed in T cell receptor (TCR) alpha mutant, TCR beta mutant, TCR beta x delta double mutant, or class II major histocompatibility complex (MHC) mutant mice, but not in recombination-activating gene RAG-1 mutant mice or nude mice kept in the same specific pathogen-free animal facility. This clinical pattern suggests that the disease requires the presence of B lymphocytes and the absence of class II MHC-restricted CD4+ alpha beta T cells. IBD in the mutant mice has some of the features of the human disease ulcerative colitis. Based on these results, we suggest that dysfunction of the mucosal immune system may underly the pathogenesis of some types of IBD in humans.
Mombaerts
P
P
Howard Hughes Medical Institute, Department of Biology Massachusetts Institute of Technology Cambridge 02139.
Mizoguchi
E
E
Grusby
M J
MJ
Glimcher
L H
LH
Bhan
A K
AK
Tonegawa
S
S
D000375:Aging; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003093:Colitis, Ulcerative / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005802:Genes, MHC Class II / Q000235:genetics*; D018398:Homeodomain Proteins; D015212:Inflammatory Bowel Diseases / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007413:Intestinal Mucosa / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D008819:Mice, Nude; D009154:Mutation; D011506:Proteins / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000172:deficiency* / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000172:deficiency / Q000235:genetics; D012007:Rectum / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology
D018398:Homeodomain Proteins; D011506:Proteins; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; C064658:RAG-1 protein