干扰素-α1b增强人γδT细胞对Daudi细胞系的细胞毒活性及相关机制  

Interferon-α1b promotes the cytotoxicity of humanγ δT cells against Daudi cell line

作　　者：党光蕾 张祥晋 张建民[1] 陈慧[1] 何维[1] DANG Guang-lei;ZHANG Xiang-jin;ZHANG Jian-min;CHEN Hui;HE Wei(Department of Immunology, Institute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC, Beijing 100005, China)

机构地区：[1]中国医学科学院基础医学研究所,北京协和医学院基础学院免疫学系,北京100005

出　　处：《基础医学与临床》2020年第5期609-614,共6页Basic and Clinical Medicine

基　　金：国家自然科学基金(81972866,31970843,81673010);国家重点研发计划(2016YFA0101001);中国医学科学院创新工程(2016-I2M-1-008);中国医学科学院T细胞与免疫治疗重点室项目(2018PT31052)。

摘　　要：目的探讨干扰素-α1b(IFN-α1b)对人γδT细胞体外杀伤肿瘤细胞的促进作用及其相关机制。方法用IFN-α1b预处理的Daudi细胞作为靶细胞;用IFN-α1b预处理的γδT细胞作为效应细胞;LDH法检测γδT细胞对Daudi细胞的细胞毒活性;ELISA检测效靶细胞混合上清中γδT细胞分泌的颗粒酶B和γ干扰素水平;流式细胞计量技术检测IFN-α1b预处理Daudi细胞表面Fas受体和应激蛋白配体ULBP3/ULBP4的表达,以及γδT细胞表面活化分子CD69和CD25的变化。结果IFN-α1b分别预处理Daudi细胞和γδT细胞都能显著增强γδT细胞对Daudi细胞的细胞毒活性(P<0.0001);IFN-α1b预处理的γδT细胞分泌颗粒酶B和γ干扰素的能力显著提高(P<0.05);IFN-α1b能上调Daudi细胞表面Fas受体和应激配体ULBP4的表达水平,而应激配体ULBP3的表达没有变化;IFN-α1b还能上调γδT细胞表面CD69的表达水平,而CD25的表达没有变化。结论IFN-α1b能通过不同的途径促进人γδT细胞对肿瘤细胞系Daudi细胞的体外细胞毒活性,两者的联用能增强γδT细胞的肿瘤治疗疗效。Objective To investigate the effect of IFN-α1b on cytotoxic activity of humanγδT cells against Daudi cells.Methods Daudi cells treated with IFN-α1b were functioned as target cells andγδT cells treated with IFN-α1b as effector cells.The cytotoxic activity ofγδT cells was tested by a lactate dehydrogenase release assay.ELISA kits were applied to detect the level of granzymes B and IFN-γreleased fromγδT cells.Flow cytometry was performed for examining Fas receptor,stress protein ligands on Daudi cells and activation markers CD69 and CD25 ofγδT cells.Results Both IFN-α1b pretreated Daudi cells orγδT cells significantly augmented the cytotoxic activity ofγδT cells against Daudi cells(P<0.0001).IFN-α1b also enhanced granzymes B and IFN-γsecretion ofγδT cells(P<0.05);IFN-α1b significantly up-regulated the expression of Fas receptor and stress ligand ULBP4 on but not ULBP3 on Daudi cells;IFN-α1b also increased the expression of CD69 but not CD25 onγδT cells.ConclusionsIFN-α1b improves cytotoxicity of humanγδT cells against cancer cell line Daudi by different mechanisms.So it is believed that IFN-α1b plusγδT cells may enhance the anti-tumor effect ofγδT cells.

关 键 词：IFN-α1b ΓΔT细胞 DAUDI细胞 细胞毒活性 

分 类 号：R392[医药卫生—免疫学]