| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon and can be divided into chronic continuous (CC-UC) and relapsing-remitting (RR-UC) types according to the clinical course. The patients with CC-UC sometimes show a failure to intensive medical treatment with prednisolone or salazosulphapyridine. In the present study, we performed functional analyzes of activated mucosal T cells using lamina propria mononuclear cells (LPMC) isolated from the UC-affected or control colonic mucosa to investigate the role of activated mucosal T cells in the refractoriness of the disease. The flowcytometric analysis showed that UCLPMC had a higher proportion of HLA-DR+T cells and this increase was more prominent in CC-UC than in RR-UC.In the follow-up study with colonoscopic biopsy samples, CC-UCLPMC continued to have higher proportions of HLA-DR+T cells whereas RR-UC LPMC exhibited decrease of their proportion during remission. The RT-PCR analysis demonstrated that the mRNA encoding IFN
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-gamma, TNF-alpha, IL-2R-alpha was almost exclusively expressed in mucosal HLA-DR+T cells but not in HLA-DR-T cells.T cell lines generated from CC-UC LPMC exhibited significantly higher activity of anti-CD3-induced cytotoxicity against a colonic epithelial cell line, HT-29 cells and production of IFN-gamma and TNF-alpha compared with those from RR-UC,and depletion experiments demonstrated that HLA-DR+T cells were mainly involved in these phenomena. These results suggested that CC-UC LPMC contained a higher percentage of activated functional T cells. Furthermore, the culture supernatant of CC-UC T cell lines induced higher expression of HLA-DR antigens on HT-29 cells than RR-UC T cell lines. Cyclosporin inhibited anti-CD3-induced cytotoxicity and cytokine production of CC-UCT cell lines in a dose-dependent manner, but either prednisolone or 5-amino salicylic acid did not induce any significant changes. In the analysis of T cell receptor Vbeta gene (Vbeta1-Vbeta20) usage with RT-PCR,there was no significant difference in the repertoire between CC-UC and RR-UC LPMC.The organ culture supernatant of UC mucosal tissues showed increased levels of inflammatory cytokines, IL-6, IL-8, G-CSF,TNF-alpha, and IL-6 was demonstrated to induce activation markers, such as IL-2R,in mucosal T cells. The results of the present study suggested that mucosal HLA-DR+T cells are polyclonally activated T cell subpopulations associated with the refractoriness of the disease. Less
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