CD277^(+/-)的备选抗原递呈细胞在γδ T细胞识别不同抗原中的限制性递呈作用  

The delivery effect of CD277^(+/-)'s alternative antigen presenting cell in the recognition of phosphorylated antigen by gamma delta T cells

作　　者：王姣 方毅敏[3,4] 梅志雄 毛玲[1,2] 申雁鸣 赖小敏[1,2] WANG Jiao;FANG Yi-min;MEI Zhi-xiong;MAO Ling;SHEN Yan-ming;LAI Xiao-min(Department of Microbiology, Zhongshan School of Medicine, Key Laboratory of Tropical Disease Control, Institute for Tuberculosis Control, Sun Yat-sen University, Guangzhou, Guangdong 510080;Guangdong Provincial Research Center for Severe Infectious Disease Prevention and Control Technology, Guangzhou, Guangdong 510080;Guangzhou Chest Hospital, Guangzhou, Guangdong 510095;State Key Laboratory of Respiratory Disease, Guangzhou, Guangdong 510095;Lingnan Hospital, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510530, China)

机构地区：[1]中山大学中山医学院微生物学教研室中山大学热带病防治研究教育部重点实验室中山大学中山医学院结核病研究所,广东广州510080 [2]广东省重大传染病预防和控制技术中心,广东广州510080 [3]广州市胸科医院,广东广州510095 [4]国家呼吸疾病重点实验室,广东广州510095 [5]中山大学附属第三医院岭南院区,广东广州510530

出　　处：《热带医学杂志》2018年第5期555-560,共6页Journal of Tropical Medicine

基　　金：国家自然科学基金(81271779);十二.五传染病重大专项分任务(2012ZX10004903-004-002);广东省自然科学基金(2014A030313725);广州市科技计划项目(155700012;201604020019)

摘　　要：目的研究CD277^(+/-)备选抗原递呈细胞(APC)在γδT细胞识别抗原中的限制性递呈作用。方法将流式分选的结核患者胸水或脐带血中的γδT细胞,用CFSE标记后与CD277^(+/-)备选抗原递呈细胞按1∶1比例混合培养,加或不加HMBPP或多肽E7刺激,使用流式细胞术检测γδT细胞增殖情况;以Transwell小室共培养法研究细胞相互接触对其增殖的影响。结果磷酸化抗原HMBPP或结核特异性多肽E7的体外刺激作用下,结核患者胸水和脐带血中的CD277^(+/-)的备选抗原递呈细胞都可引起γδT细胞不同程度的活化增殖,且CD277^+细胞的活化作用强于CD277^-细胞。不同个体来源的单核细胞系的备选APCs相对于淋巴细胞系的备选APCs更容易引起γδT细胞的增殖,其中以CD1a^+CD277^+CD14^-CD1b^-CD1c^-的细胞的抗原递呈效应最为明显,且通过小室实验证实了γδT细胞的增殖过程需与APCs相接触来实现。结论 CD277分子对γδT细胞识别不同抗原有一定限制性递呈作用,需进一步研究相关分子机制从而为γδT细胞的抗结核免疫机制以及相关的免疫治疗提供依据。Objective To investigate the function of the potential CD277^＋/-antigen presenting cells（APC）in the recognition of the phosphoantigens by γδ T cells. Methods γδT cells and CD277^＋/-APC were sorted from the neonatal umbilical cord blood or the pleural fluid（PLF）of the tuberculosis（TB）patients by using the fluorescence activated cell sorting（FACS）.CFSE labled γδ T cells were co-cultured with the alternative APC at a stoichiometry of 1∶1 in the absence or presence of the phosphoantigens（HMBPP）or peptide E7. Expansion ratios were measured by flow cytometry. To examine whether potential CD277^＋/-antigen presenting cells induce γδ T cells proliferation in vitro either via cell to cell contact or soluble factors,γδT cells were co-cultured with CD14＋CD277^＋ cells in a transwell system. Results Under the stimulation of phosphoantigens（HMBPP） or MTB-specific peptides（E7）,CD277^＋/-alternative APCs in neonatal umbilical cord blood or pleural fluid of TB patients could cause γδ T cells activated and proliferated in different levels. CD277^＋ cells showed better antigen-presenting effects than CD277-- cells. APCs from monocytes were more easily to cause activation of the γδ T cells than those from lymphocytes and CD1a^＋CD277^＋CD14-CD1b^-CD1c^-cells showed the best antigen-presenting effects. We also found that a cellto-cell interaction between γδT cells and APCs is required for the induction of their proliferation by a transwell system.Conclusion CD277 molecule plays a restrictive role in γδT cells to recognize the distinct antigens. The study may have implications for γδT cell-based immunotherapeutic strategies.

关 键 词：γδ T细胞 单核-巨噬细胞 抗原递呈细胞 HMBPP CD277 

分 类 号：R446.6[医药卫生—诊断学]