细胞膜异位表达钙网蛋白的CD4^+T细胞诱导EAE小鼠保护性免疫  

Calreticulin expression is necessary for protective immune effect of T-cell vaccine in EAE mice

作　　者：周湧 李心群[2] 李金亭 许文 ZHOU Yong;LI Xin-qun;LI Jin-ting;XU Wen(Department of Clinical Laboratory, The Fifth People’s Hospital of Dongguan, Dongguan 523899, China;The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325035, China;School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, China)

机构地区：[1]东莞市第五人民医院检验科,广东东莞523899 [2]温州医科大学附属第一医院,浙江温州325035 [3]温州医科大学基础医学院,浙江温州325035

出　　处：《中国病理生理杂志》2019年第4期744-748,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81571624);温州市科技局资助项目(No.Y20150004)

摘　　要：目的:研究细胞膜表面异位表达钙网蛋白(calreticulin,CALR)对T细胞疫苗(T-cell vaccine,TCV)诱导的保护性免疫效果的影响。方法:采用小鼠髓鞘少突胶质细胞糖蛋白35-55(MOG_(35-55))免疫C57BL/6小鼠建立实验性自身免疫性脑脊髓炎(EAE)模型,分别以MOG_(35-55)特异性T细胞(CALR^+T及CALR^-T)为疫苗,通过尾静脉注射免疫小鼠。检测指标包括EAE小鼠临床评分比较、脾CD4^+ CD25^+ Foxp3^+调节性T细胞百分比测定及血清中细胞因子干扰素γ(IFN-γ)、白细胞介素4(IL-4)、IL-10和IL-17A含量测定。结果:射线照射可诱导活化CD4^+T细胞表面异位表达CALR;CALR^+T免疫组症状显著轻于CALR^-T免疫组(P<0.01);CALR^+T免疫组小鼠脾CD4^+ CD25^+ Foxp3^+调节性T细胞百分比及血清中IL-4和IL-10含量显著高于对照组(P<0.01),而IFN-γ和IL-17A含量显著低于对照组(P<0.01),结论:细胞膜表面异位表达CALR与TCV诱导的保护性免疫效果有关。AIM: To study the role of cell membrane ectopic calreticulin(CALR) expression on the protective immunie effect of T-cell vaccine(TCV) on experimental autoimmune encephalomyelitis(EAE). METHODS: EAE model was established by myelin oligodendrocyte glycoprotein 35-55(MOG35-55) immunization in C57 BL/6 mice, and the mice were immunized with MOG35-55-specific CALR^+ and CALR- T-lymphocytes. Symptomatic scores were compared at the maximum of the disease. On the 15 th day after immunization, the proportion of CD4^+ CD25^+ Foxp3^+ regulatory T cells(Treg) in the spleen, and the expression of interferon-γ(IFN-γ), interleukin-4(IL-4), IL-10 and IL-17 A in the serum were measured. RESULTS: Increased expression of CALR in activated T cells after γ-irradiation was observed. Blockade of CALR on the vaccinating T-cell surface reduced the protective effect of TCV. Furthermore, blockade of CALR reduced the number of Treg in the spleen and up-regulated pro-inflammatory cytokines. CONCLUSION: CALR expression in the T cells is necessary for the protective immunity induced by TCV in EAE mice.

关 键 词：钙网蛋白 实验性自身免疫性脑脊髓炎 T细胞疫苗 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学] R593[医药卫生—基础医学]