Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
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Research Abstract |
We analyzed ulcerative colitis from the standpoint of lymphocytic expansion in the loco by immunohistochem- istry and flow cytometry. Ulcerative colitis was character- ized by a diffuse distribution of Ki-67+ small round cells particularly in the ulcer base (that were CD19+ and CD20-), with a significant number of them also CD138+. Immuno- electron microscopy for CD19 revealed an abundance of rough endoplasmic reticulum in the cytoplasm. These in- dicated that they are of immature plasma lineage cells. By contrast, plasma cells in Crohn's disease were negative for CD19, and the labeling for Ki-67 was infrequent, showing mature phenotype. Flow cytometry revealed an occurrence of CD19+ and CD20- cells in ulcerative colitis but not in Crohn's disease. The labeling index of Ki-67 among CD19+ plasma cells was positively correlated with the clinical activity of ulcerative colitis. High labeling of Ki-67 in CD19+ plasma cells is specific for active ulcerative colitis that was resistant to med
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ical treatment by corticosteroids. Next, We investigated he Th1 response and SLC and ELC in Crohn's disease pathogenesis immunohistochemicaly. ELC was almost undetectable in intestinal samples. SLC was found sporadically in lymphoid follicles, lymphoid aggregate venules, and lymphatic vessels. In mesenteric lymph nodes (MLNs), SLC was highly expressed in high endothelial venules (HEVs), lymphatic vessels, and stromal Dendritic cells (DCs), predominantly in T cell areas. ELC was highly expressed in mature DCs. There were significantly more SLC positive HEVs and ELC positive mature DCs, important components of T cell areas, in Crohn's disease. SLC, ELC, and CCR7 mRNA was significantly higher in Crohn's disease MLNs compared with Ulcerative colitis. Crohn's disease MLNs had increased expression of SLC and ELC, mainly in HEVs, mature DCs, and lymphatic vessels, inducing T cell hyperplasia. CCR7 mRNA was increased in T cell areas. The dominant Th1 immune response is facilitated by interaction of SLC positive HEVs/lymphatic vessels, ELC positive mature DCs, and CCR7 positive T cells in hyperplastic T cell areas. In Crohn's disease, memory T cells and mature DCs may home to MLN Less
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