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

基础医学与临床 ›› 2020, Vol. 40 ›› Issue (5): 609-614.

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

党光蕾, 张祥晋, 张建民, 陈慧^*, 何维^*

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

收稿日期:2020-01-14 修回日期:2020-03-18 出版日期:2020-05-05 发布日期:2020-04-30
通讯作者: *heweingd@126.com; chenhui_1980@126.com
基金资助:
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)

Interferon-α1b promotes the cytotoxicity of human γδT cells against Daudi cell line

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

Received:2020-01-14 Revised:2020-03-18 Online:2020-05-05 Published:2020-04-30
Contact: *heweingd@126.com; chenhui_1980@126.com

摘要/Abstract

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。结果 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。

关键词: IFN-α1b, γδT细胞, Daudi细胞, 细胞毒活性

Abstract: Objective To investigate the effect of IFN-α1b on cytotoxic activity of human γδT cells against Daudi cells. Methods Daudi cells treated with IFN-α1b were functioned as target cells and γδT cells treated with IFN-α1b as effector cells. The cytotoxic activity of γδT cells was tested by a lactate dehydrogenase release assay. ELISA kits were applied to detect the level of granzymes B and IFN-γ released from γδT cells. Flow cytometry was performed for examining Fas receptor, stress protein ligands on Daudi cells and activation markers CD69 and CD25 of γδT cells. Results Both IFN-α1b pretreated Daudi cells or γδT cells significantly augmented the cytotoxic activity of γδT cells against Daudi cells (P＜0.0001). IFN-α1b also enhanced granzymes B and IFN-γ secretion of γδT 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 on γδT cells. Conclusions IFN-α1b improves cytotoxicity of human γδT cells against cancer cell line Daudi by different mechanisms.So it is believed that IFN-α1b plus γδT cells may enhance the anti-tumor effect of γδT cells.

Key words: IFN-α1b, γδT cells, Daudi cells, cytotoxicity

中图分类号:

R392

党光蕾, 张祥晋, 张建民, 陈慧, 何维. 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[J]. 基础医学与临床, 2020, 40(5): 609-614.

DANG Guang-lei, ZHANG Xiang-jin, ZHANG Jian-min, CHEN Hui, HE Wei. Interferon-α1b promotes the cytotoxicity of human γδT cells against Daudi cell line[J]. Basic & Clinical Medicine, 2020, 40(5): 609-614.

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