1996 Fiscal Year Final Research Report Summary
ANALYSIS OF ACTIVATED MUCOSAL TCELLS IN ULCERATIVE COLITIS PATIENTS
| Project/Area Number |
07670583
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | NAGOYA UNIVERSITY |
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Principal Investigator |
KUSUGAMI Kazuo SCHOOL OF MEDICINE,NAGOYA UNIVERSITY SENIOR LECTURER, 医学部, 助手 (00234427)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUURA Toshihiro SCHOOL OF MEDICINE,NAGOYA UNIVERSITY STAFF, 医学部, 医員
SHINODA Masataka SCHOOL OF MEDICINE,NAGOYA UNIVERSITY STAFF, 医学部, 医員
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| Project Period (FY) |
1995 – 1996
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| Keywords | ulcerative colitis / chronic continuous / lamina propria mononuclear cells / HLA-DR-positve T cells / IFN-gamma / TNF-alpha |
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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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