小鼠嗜碱性细胞肝内高表达并辅助初始CD4＋T细胞向Th2应答偏极化  

Murine basophils express highly in fiver and regulate priming of naive CD4＋ T cells to develop into Th2 cells

作　　者：许强[1] 屠静[2] 沈弢[1] 

机构地区：[1]北京大学医学部基础医学院病原生物学系,100191 [2]北京大学感染病研究所,100191

出　　处：《中华微生物学和免疫学杂志》2012年第8期673-678,共6页Chinese Journal of Microbiology and Immunology

基　　金：北京市自然科学基金面上项目（7122108）;教育部2010年度高等学校博士学科点专项科研基金（20100001120047）

摘　　要：目的比较嗜碱性细胞在小鼠多器官内分布水平，并分析肝脏嗜碱性细胞参与CD4^＋T细胞分化的免疫特征。方法分离小鼠外周血、肝脏、脾脏、肺和淋巴结中单个核白细胞群，比较研究FcsRI^＋CD49b^＋细胞在单个核白细胞中的比例水平。免疫磁珠分选肝脏嗜碱性细胞后体外多种不同细胞因子共培养24h，检测嗜碱性细胞的凋亡水平。IL-3通过渗透压微泵皮下稳定刺激小鼠1周后比较分析嗜碱性细胞在肝脏内白细胞中比例水平。最后检测嗜碱性细胞通过分泌细胞因子的方式影响初始CD4^＋T细胞向Th1／Th2分化状态的特征。结果生理状态下小鼠嗜碱性细胞在肝脏中单个核白细胞中的比例显著高于外周血、脾脏、肺和淋巴结。IL-3在体外体内试验均证明可抑制嗜碱性细胞的凋亡，延长细胞寿命。嗜碱性细胞可通过分泌细胞因子的方式诱导初始CD4^＋T细胞向Th2应答偏极化并抑制Th1免疫应答。结论嗜碱性细胞可增强Th2免疫应答和抑制Th1免疫应答，结合嗜碱性细胞在肝脏中高表达的事实，提示嗜碱性细胞可能参与肝脏特有的生理性免疫耐受状态的构成。Objective To compare the levels of murine basophils distribution in different organs and analyze the characteristics of CD4＋ T ceils activation/differentiation regulated by basophils. Methods Firstly, the mononuclear leukocytes were isolated separately from periphery blood, liver, spleen, lung and lymph nodes and the percentages of FcsR I ＋ cIMgb＋ basophils in different organs were investigated. Secondly, liver ba- sophils were purified by immuno-microbead strategy and co-clutured with different cytokines for 24 h. Apoptosis status of basophils was detected by Annexin V straining method. Thirdly, Mice were subcutaneously implanted with a miniosmotic pump containing 5 p,g IL-3. At day 7 after implantation, liver mononuclear cells were harves- ted and the percentages of basophils were analyzed. Finally, Thl/Th2 polarization influenced by basophils ori- entated cytokines was investigated when naive OT- II CD4 T cells were stimulated with spleen dentritic cells and OVA peptides. Results The percentage of murine basophils in mononuclear leukocytes of liver was significantly higher than that of periphery blood, spleen, lung and lymph nodes under physiological condition. Both of in vitro and ex vivo experiments showed that IL-3 played an inhibitory role on apoptosis of basophils. Cytokines secreted by basophils was investigated to induce Th2 polarization and inhibit Thl response when naive OT- 1I CD4 T cells were co-cultured with spleen dentritic cells and OVA peptides. Conclusion Th2 response was enhanced and Thl response was down-regulated by murine basophils, which implied that basophils might participate in the construction of liver specific physiological immuno-tolerant microenvironment.

关 键 词：嗜碱性细胞 肝脏 Th2免疫应答 凋亡 

分 类 号：R392[医药卫生—免疫学]