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肾小管上皮细胞表达共刺激分子B7-DC并抑制CD4^+ T细胞活化 被引量：1

Inhibitory effects of costimulatory molecule B7-DC expressed in renal tubular epithelial cells on CD4^+ T cell activation
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摘要 目的探讨肾小管上皮细胞(TECs)表达B7-DC及其对T细胞活化的调节作用。方法免疫组化检测肾穿刺标本B7-DC表达;流式细胞术分析人及小鼠肾小管上皮细胞B7-DC的表达变化;使用TECs/CD4+ T共培养分析TECs表达的B7-DC对CD4+ T细胞活化的影响。结果慢性肾小球肾炎、狼疮性肾炎、小管间质性肾炎等肾活检组织中发现B7-DC显著表达于肾小管。IFN-γ、TNF-α等炎症因子可诱导体外肾小管上皮细胞表达B7-DC。共培养试验发现阻断B7-DC信号可增强CD4+ T细胞分泌细胞因子IFN-γ及IL-2并促进CD4+ T细胞表达CD69。结论肾小管上皮细胞表达B7-DC并可显著下调CD4+ T细胞活化,在多种慢性肾脏疾病发展中可能发挥重要作用。 Objective To detect the potential role of B7-DC, a novel immune co-stimulatory molecule, in the pathogenesis of nephritis. Methods Immunohistochemical analysis was used to detect B7-DC in normal or diseased human kidney samples. Furthermore, coculture experiment was performed to confirm the role of TEC-related B7-DC in regulating CD4^＋ T cell activation. Results Immunohistochemical analysis revealed that B7-DC was specifically expressed on tubular epithelial cells （TEC） of diseased human kidney samples, including chronic glomerulonephritis, lupus nephritis, tubulointerstitial nephritis, and renal cell carcinoma. Co-culture demonstrated that human TEC-related B7-DC was a strong inhibitor of CD4^＋ T cell activation confirmed by increasing cytokines （interferon-7 and interleukin- 2） production and enhancing the level of T-cell activation marker CD69 in presence of MIH18, a blocking antibody of B7-DC. Conclusion B7-DC might play a central role in maintaining peripheral tolerance, protecting the epithelium from immune-mediated tubulointerstitial injury. Furthermore, blocking B7-DC signal might benefit the immunotherapy of renal carcinoma.
作者 王志成 阮志华 王长松 费蕾 陈鹿鹿 吴玉章 张镜波 陈永文
机构地区 解放军 第三军医大学附属西南医院肿瘤科 解放军 第三军医大学全军免疫学研究所 第三军医大学附属新桥医院肾内科
出处 《免疫学杂志》 CAS CSCD 北大核心 2008年第5期572-575,578,共5页 Immunological Journal
基金 国家自然科学基金资助项目(30571700及30600546)
关键词 B7-DC 肾小管上皮细胞 Program death-1 共培养 B7-DC Renal tubular epithelial cells Program death-1 Co-culture experiment
分类号 R392 [医药卫生—免疫学]
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参考文献12

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免疫学杂志
2008年 第5期

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