SPONTANEOUS DEVELOPMENT OF INFLAMMATORY BOWEL-DISEASE IN T-CELL RECEPTOR MUTANT MICE

被引:632
作者
MOMBAERTS, P
MIZOGUCHI, E
GRUSBY, MJ
GLIMCHER, LH
BHAN, AK
TONEGAWA, S
机构
[1] HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT PATHOL, BOSTON, MA 02114 USA
[2] HARVARD UNIV, SCH PUBL HLTH, DEPT CANC BIOL, BOSTON, MA 02115 USA
[3] HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02115 USA
[4] MASSACHUSETTS GEN HOSP, CTR STUDY INFLAMMATORY BOWEL DIS, BOSTON, MA 02114 USA
[5] NEW ENGLAND REG PRIMATE RES CTR, BOSTON, MA 02114 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1016/0092-8674(93)80069-Q
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 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 dysfunction of the mucosal immune system may underly the pathogenesis of some types of IBD in humans.
引用
收藏
页码:275 / 282
页数:8
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