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 target ing in embryonic stem cells. Chronic colitis was observed in T cell re ceptor (TCR) alpha mutant, TCR beta mutant, TCR beta x delta double mu tant, or class II major histocompatibility complex (MHC) mutant mice, but not in recombination-activating gene RAG-1 mutant mice or nude mic e kept in the same specific pathogen-free animal facility. This clinic al pattern suggests that the disease requires the presence of B lympho cytes and the absence of class II HC-restricted CD4+ alphabeta 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 dysfuncti on of the mucosal immune system may underly the pathogenesis of some t ypes of IBD in humans.