INFLAMMATORY BOWEL-DISEASE IN C.B-17 SCID MICE RECONSTITUTED WITH THECD45RB(HIGH) SUBSET OF CD4(-CELLS() T)

Chronic inflammation developed spontaneously in the large intestine of C.B-17 sicd mice restored with the CD45RB(high) subset of CD4(+) T ce lls obtained from normal BALB/c mice. The inflammation, which extended diffusely from the cecum to the rectum, was localized to the lamina p ropria of mildly affected mice but became transmural in severely affec ted mice. Immunohistochemical and flow cytometric analyses showed that the inflammatory infiltrate contained numerous macrophages accompanie d by moderate numbers of activated CD4(+) lymphocytes. Some mice also had scattered multinucleated giant cells. Mucin depletion and epitheli al hyperplasia resulting in glandular elongation and mucosal thickenin g were also consistently seen. Less frequent findings included ulcerat ion with fibrosis, crypt abscesses, crypt loss, adn granulomatous infl ammation. Immunofluorescent analysis of inflamed large intestinal sect ions demonstrated increased epithelial expression of major histocompat ibility class II antigens. The changes in the large intestine of these mice are similar to those seen in patients with idiopathic inflammato ry bowel disease (Crohn's disease and ulcerative colitis). This murine model may be useful for studying mucosal immunoregulation as it relat es to the pathogenesis and treatment of chronic inflammatory bowel dis eases in the large intestine of human patients.