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自体胃癌组织总RNA转染DC诱导的CTL对转染肿瘤组织和正常组织总RNA的DC致伤作用

THE CYTOTOXICITY OF CYTOTOXIC T-LYMPHOCYTES PRIMED WITH DENDRITIC CELLS LOADED BY RNA OF GASTRIC CANCER TISSUE TO DENDRITIC CELLS LOADED BY RNA OF GASTRIC CANCER TISSUE AND BY RNA OF NORMAL GASTRIC TISSUE

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【作者】 林林李桂馨张占学周保军蔡建辉刘津

【Author】 LIN Lin,LI Guixin,ZHANG Zhanxue.ZHOU Baojun,CAI Jianhui,LIU Jin~* (Department of Gastrointestinal Surgery,the Second Hospital of Hebei Medical University,Shijiazhuang 050000,China)

【机构】 河北医科大学第二医院胃肠外科

【摘要】 目的证实并比较胃癌自体肿瘤组织总RNA转染树突状细胞(dendritic cell,DC)诱导的细胞毒性T淋巴细胞(cytotoxic T-lymphoeytes,CTL)对肿瘤组织和正常组织总RNA转染DC的致伤作用。方法用脂质体转染的方法将3例胃癌患者肿瘤组织总RNA和正常组织总RNA转染到其自体单个核细胞源性DC中,以肿瘤组织总RNA转染DC(DC/Tumor RNA)致敏T淋巴细胞得到CTL,以calcein-AM细胞毒试验和酶联免疫斑点法测定干扰素-γ(interferon-γ,IFN-γ)分泌来检测CTL对肿瘤组织和正常组织总RNA转染DC的溶细胞效果。结果 CTL对DC/Tumor RNA杀伤率与对转染正常组织总RNA的DC(DC/Normal RNA)杀伤率比较差异有统计学意义(P<0.05)。DC/Tumor RNA组CTL分泌IFN-γ较DC/Normal RNA组高出近2倍(P<0.05)。结论转染肿瘤组织总RNA的DC提高了抗肿瘤CTL的细胞毒作用,同时也诱导CTL对正常组织的致伤作用,以期降低DC为基础的肿瘤免疫治疗对正常组织的致伤作用提供理论依据。

【Abstract】 Objective To identify the cytotoxic capability of cytotoxic T - lymphocytes ( CTL) to dendritic cells (DCs) loaded with normal tissue RNA and DCs loaded with total tumor RNA, which is induced by DCs loaded with total tumor RNA. Methods Monocytes - derived DCs were transfected with either total tumor RNA or normal RNA of 3 patients with gastric cancer. T cells were primed with tumor RNA transfected DCs and cytolytic effects of the generated CTL were measured with Cytotoxicity assay and interferon - γ (IFN-γ) release elispot assay. Results Cytotoxicity against DCs loaded with tumoral RNA was significantly different from that against normal RNA - loaded DCs (P < 0. 05 ). The INF - γ secretion was more than 2 - folds higher in tumoral RNA - loaded DCs when compared with normal RNA - loaded DCs (P < 0. 05 ). Conclusion DCs loaded with tumoral RNA improve the cytotoxicity of the CTL, but the CTL primed with DCs loaded with tumoral RNA can injury the normal tissue. This experience proved the theory evidences to construct CTL primed with DCs loaded with differential displaying cDNA which will maintain the cytotoxicity to tumor and remove the damage to normal tissue.

【基金】 河北省2011年医学科学研究重点课题计划(20110346)
  • 【文献出处】 河北医科大学学报 ,Journal of Hebei Medical University , 编辑部邮箱 ,2011年11期
  • 【分类号】R735.2
  • 【下载频次】22
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