约氏疟原虫感染小鼠肺组织TIGIT^(+)CD8^(+)T细胞数量增加但细胞因子分泌能力降低  

The number of TIGIT^(+)CD8^(+)T cells increasess but theirr cytokine secretion decreases in the lungs of Plasmodium yoeli infected mice

作　　者：谢安琪 黎家杰 方超 石飞虎 邢俊敏 莫峰 谢红艳 黄俊 魏海霞 XIE Anqi;LI Jiajie;FANG Chao;SHI Feihu;XING Junmin;MO Feng;XIE Hongyan;HUANG Jun;WEI Haixia(Department of Pathogen Biology and Immunology,School of Basic Medical Sciences,Guangzhou Medical University,Guangzhou 511436,China)

机构地区：[1]广州医科大学基础医学院病原生物学与免疫学教研室,广东广州511436

出　　处：《细胞与分子免疫学杂志》2023年第8期673-679,共7页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家自然科学基金青年科学基金(81802024);广东省自然科学基金(2021A151501103,2020A1515010251);广州市科技计划(202002030082)。

摘　　要：目的研究含免疫球蛋白和免疫受体酪氨酸抑制基序结构域T细胞免疫受体(TIGIT)对疟原虫感染小鼠肺脏中CD8^(+)T细胞功能的影响。方法约氏疟原虫(Plasmodium yoelii)感染小鼠12 d后,分离肺脏,称体质量,拍照;消化后分离肺脏淋巴细胞,计数、染色,流式细胞术检测CD8^(+)、TIGIT^(+)CD8^(+)T细胞的含量;流式细胞术检测TIGIT^(+)CD8^(+)T细胞的L选择素(CD62L)、CD69、程序性死亡蛋白1(PD-1)、CD25和CX3C趋化因子受体1(CX3CR1)的表达情况;佛波酯(PMA)和离子霉素刺激后,检测TIGIT^(+)CD8^(+)T细胞分泌γ干扰素(IFN-γ)、白细胞介素21(IL-21)、IL-4、IL-17和IL-10的能力。结果疟原虫感染小鼠体质量减轻,肺脏变黑变暗,肺脏质量和占体质量比明显增加。与正常组小鼠相比,疟原虫感染后小鼠肺组织CD8^(+)T细胞和TIGIT^(+)CD8^(+)T细胞百分比和绝对数量显著升高。与正常小鼠TIGIT^(+)CD8^(+)T细胞相比,感染组TIGIT^(+)CD8^(+)T细胞中表达CD62L的细胞百分比显著降低,表达CD69、PD-1、CX3CR1的细胞百分比显著升高,感染组TIGIT^(+)CD8^(+)T细胞可分泌IL-21、IL-4、IL-17、IL-10的细胞百分比显著降低。结论疟原虫感染后,小鼠肺脏病变明显,TIGIT^(+)CD8^(+)T细胞数量增加,该细胞群表达多种活化相关分子,但分泌细胞因子的能力降低。Objective To investigate the effect of T cell immunoreceptor with Ig and ITIM domains(TIGIT)on the function of CD8^(+)T cells in the lungs of Plasmodium infected mice.Methods The lungs of the mice infected with Plasmodium yoeli were isolated,weighed and photographed after 12 days'infection.After dissolution,lung lymphocytes were isolated,counted and stained,and then the contents of CD8^(+)and TIGIT^(+)CD8^(+)T cells were detected by flow cytometry.The expressions of L selectin((CD62L),CD69,programmed death 1((PD-1),CD25,and C-X3-C motif chemokine receptor 1(CX3CR1)on TIGIT^(+)CD8^(+)T cells were detected by flow cytometry.After stimulation with phorbol 12-myristate 13-acetate(PMA)and ionomycin,the ability of TIGIT^(+)CD8^(+)T cells to secrete interferon(IFN-),interleukin 21(IL-21),IL-4,IL-17,and IL-10 was detected.Results The body mass of mice with Plasmodium infection was reduced.The lungs became darker,and the ratio of the lung mass to body mass was significantly increased.Compared with the normal mice,the percentages and absolute quantity of CD8 and TIGIT CD8^(+)T cells in the lungs of the infected mice were significantly increased.The percentage of TIGIT^(+)CD8^(+)T cells expressing CD62L in the infected group was significantly lower,while the percentage of the CD69,PD-1,and CX3CR1 cells were significantly higher than that of TIGIT^(+)CD8^(+)T cells from the normal mice.The percentages of TIGIT^(+)CD8^(+)T cells secreting IL-21,IL-4,IL-17 and IL-10 cells in the infected group were significantly lower.Conclusion The lung lesions from mice with Plasmodium infection are obvious,the numbers of TIGIT^(+)CD8^(+)T cells increase,and these cells express a variety of activation-related molecules,but the ability to secrete cytokines is reduced.

关 键 词：约氏疟原虫(Plasmodium yoelii) 肺脏 CD8^(+)T淋巴细胞 含免疫球蛋白和免疫受体酪氨酸抑制基序结构域T细胞免疫受体(TIGIT) 

分 类 号：R382.31[医药卫生—医学寄生虫学] R531.3[医药卫生—基础医学] R331.144