Mombaerts P, Mizoguchi E, Grusby M J, Glimcher L H, Bhan A K, Tonegawa S
Howard Hughes Medical Institute, Department of Biology Massachusetts Institute of Technology Cambridge 02139.
Cell. 1993 Oct 22;75(2):274-82. doi: 10.1016/0092-8674(93)80069-q.
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.
我们描述了通过胚胎干细胞基因靶向创建的几种免疫缺陷小鼠品系中炎症性肠病（IBD）的自发发展情况。在T细胞受体（TCR）α突变体、TCRβ突变体、TCRβxδ双突变体或II类主要组织相容性复合体（MHC）突变体小鼠中观察到慢性结肠炎，但在饲养于同一特定病原体-free动物设施中的重组激活基因RAG-1突变体小鼠或裸鼠中未观察到。这种临床模式表明，该疾病需要B淋巴细胞的存在以及II类MHC限制性CD4+αβT细胞的缺失。突变体小鼠中的IBD具有人类疾病溃疡性结肠炎的一些特征。基于这些结果，我们认为黏膜免疫系统功能障碍可能是人类某些类型IBD发病机制的基础。
