OBJECTIVES: Epithelioid granulomas with transmural inflammation are a characteristic histological feature in Crohn's disease (CD). However, these are not frequently detected by histopathological examination in the biopsy specimens. Here, we demonstrated unique structures with T-lymphocyte aggregates (TLAs) that were specifically found in ileal villi of CD. We characterized the histological and phenotypical features of these structures and assessed the diagnostic value of TLAs for CD. METHODS: Tissue samples were obtained from the inflamed and uninflamed areas of ileal and colonic mucosa of 32 patients with CD. For controls, mucosal samples were obtained from unaffected areas of 18 patients with colon cancer and inflamed and uninflamed areas of 12 patients with ulcerative colitis (UC). RESULTS: 1) In 21 of 32 cases of CD (66%), we found unique structures with lymphoid cell aggregates that were localized in villi of ileum. These structures were not detected in any normal or UC intestine. 2) These structures were composed mainly of T cells, and CD4+ CD45RO+ cells dominated. Neither B cells nor c-kit positive immature lymphocytes were found. Moreover, CD68 positive macrophages were demonstrated in these aggregates, and cells positive for interleukin 18, a pivotal cytokine for Th1 differentiation, were expressed. 3) The aggregates were detected in seven of 13 patients with CD in whom granuloma was not detected by precise histopathological examination. Furthermore, we detected TLAs even in the ilea of two of four CD patients (50%) whose affected lesions were limited to the colon. CONCLUSIONS: We demonstrated TLAs in intestinal villi that may contribute to the pathogenesis of CD. Detection of these lymphocyte aggregates is helpful for diagnosis of CD when granuloma is not found.
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