Role of appendix in the development of inflammatory bowel disease in TCR-α mutant mice

Abstract

T cell receptor-α mutant mice (TCR-α(-/-)), created by gene targeting of the TCR-α gene in embryonic cells, spontaneously inflammatory bowel disease (IBD) resembling human ulcerative colitis. Since gut-associated lymphoid tissue is likely to play an important role in the development of chronic intestinal inflammation, we examined the changes in the appendix lymphoid follicle (ALF) and Peyer's patches (PP) in these mice. We found the structure of the ALF to the remarkably similar to that of the PP in the small intestine; in both instances, lymphoid follicles covered by surface epithelium (dome-formation) were found. The amount of proliferation in the lymphoid follicles of the appendix estimated by in vivo incorporation of 5- bromo-2' deoxyuridine was more than two times of PP in TCR-α(-/-) mice. ELISPOT assay showed an increase of IgA, IgG1, and IgG2a, but not IgM- secreting B cells in ALF of TCR-α(-/-) mice compared to TCR-α(+/-) control mice. Furthermore, TCR-α(-/-) mice revealed an increase of autoantibody- producing B cells against the cytoskeletal protein tropomyosin in ALF as compared to PP. When TCR-α(-/-) mice underwent appendectomy at a young age (3-5 wk), the number of mesenteric lymph node cells at 6-7 mo were markedly less than in the sham-operated TCR-α(-/-) mice. Furthermore, appendectomy at 1 mo of age suppressed the development of IBD, with only 3.3% of these mice developing IBD in the 6-7-mo period of observation. In contrast, ~80% of controls, including the sham-operated TCR-α(-/-) mice, developed IBD during this period. These results suggest that ALF, rather PP is the priming site of cells involved in the disease process and plays an important role in the development of IBD in TCR-α(-/-) mice.