共刺激因子在溃疡性结肠炎中的表达及意义
Expression of co-stimulators in ulcerative colitis and its pathologic significance
摘要目的 探讨共刺激因子及淋巴细胞亚型与溃疡性结肠炎活动性的关系,以及在肠黏膜中的分布特征及其与溃疡性结肠炎发病的关系.方法 采用免疫组织化学EnVision法检测溃疡性结肠炎活动期(64例)、缓解期(51例)及正常结肠黏膜(20例)石蜡标本中共刺激因子CD86和可诱导共刺激因子(ICOS)的表达及分布;检测9例溃疡性结肠炎患者(7例活动期,2例缓解期)及5例正常对照结肠黏膜的冷冻标本中共刺激因子CD28的表达及分布.同时检测CD4、CD8和CD20阳性淋巴细胞在肠黏膜中的分布,分析其与共刺激因子表达间的关系.结果 共刺激因子CD86在固有膜淋巴单核细胞及肠上皮细胞中的表达为活动期>缓解期>对照组(P<0.05或P<0.01);而ICOS在固有膜淋巴单核细胞表达为活动期高于缓解期及对照组,ICOS在肠上皮细胞表达为活动期高于缓解期(P<0.01).CD28表达为活动期高于缓解期及对照组(P<0.05或P<0.01).固有膜间质、上皮细胞问及小血管壁CD4~+辅助性T淋巴细胞和CD8~+细胞毒性T淋巴细胞的数量、CD4/CD8比值,以及CD20~+ B淋巴细胞数量均为活动期高于缓解期及对照组(P<0.01).结论 共刺激因子CD86、ICOS在溃疡性结肠炎肠上皮细胞和固有膜淋巴单核细胞中存在表达上调现象,提示共刺激因子的异常表达可能参与了溃疡性结肠炎发病过程中细胞免疫和体液免疫的过度激活.
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abstractsObjective To study the expression and localization of co-stimulators in the mueosa of patients with ulcerative colitis ( UC) , and to explore its role in the pathogenesis of UC. Methods Expression of co-stimulators CD86 and inducible co-stimulator (ICOS) was studied by immunohistochemistry on paraffin-embedded mucosal tissue from patients with active UC (64 cases) , inactive UC (51 cases) and normal controls (20 cases). Immunostaining for CD28 was also carried out on frozen fresh mucosal tissue sampled from patients with active UC (7 cases) , inactive UC (2 cases) and normal controls (5 cases). In addition, expression of CD4, CD8 and CD20 were also examined. Results In active UC, increased expression of CD86 was not only observed in lamina propria mononuclear cells but also in the intestinal epithelial cells, as compared with inactive UC and the normal controls (P < 0. 01 ) . Increased ICOS expression in lamina propria mononuclear cells was detected in active UC, as compared with inactive UC and the normal controls (P<0. 01). Increased ICOS expression in intestinal epithelial cells was also seen in active UC, as compared with that of inactive UC ( P < 0. 01 ). The expression of CD86 was higher in inactive UC than in the normal controls ( P < 0. 05 or P < 0. 01 ) . However, the expression of ICOS showed no statistically significant difference between inactive UC and normal controls. Increased expression of CD28 in active UC, compared with that in inactive UC and normal controls, was also noticed ( P < 0. 05 or P < 0. 01). The number of CD4 or CD8-positive intraepithelial lymphocytes and lymphocytes infiltrating in the lamina propria and small vessel walls was much higher in active UC than in inactive UC and normal controls ( P < 0. 01). Moreover, the ratio of CD4/CD8 was highest in active UC (P < 0. 01). The number of CD20-positive B lymphocytes in lamina propria was also higher in active UC than in inactive UC and normal controls (P < 0. 01). Conclusions In active UC, CD86 and ICOS were over-expressed in the intestinal epithelial cells and lamina propria mononuclear cells. The phenomenon suggests that abnormal expression of co-stimulators may contribute to the deregulation of acquired immune responses in UC.
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