移植物抗宿主病小鼠肝脏及异体CD8^+T细胞趋化因子和趋化因子受体表达分析

Chemokines and chemokine receptors expressed by the liver and allo-reactive CD8^+ T cells in graft-versus-host disease mouse

为探讨趋化因子及其受体介导的效应性细胞迁移在移植物抗宿主病(graft-versus-host disease,GVHD)发生发展中的重要作用,采用次要组织相容性抗原异配的GVHD小鼠模型,应用流式细胞分选术(FACS)、实时荧光定量聚合酶链反应等方法,分析GVHD靶器官和异体CD8+T细胞趋化因子及受体的表达。肝脏高表达干扰素诱导蛋白-10(IP-10)、干扰素诱导的T细胞趋化因子(ITAC)、γ干扰素诱生单核因子(MIG)、巨噬细胞炎症蛋白(MIP)-1α/β等趋化因子。异体CD8+T细胞上则高表达CXC趋化因子受体(CXCR)3和CC趋化因子受体(CCR)5。随着肝脏趋化因子的表达增加,异体CD8+T细胞迁移浸润的数量也增高。因而趋化因子及异体CD8+T细胞上趋化因子受体的特异对应关系,促使大量异体CD8+T细胞迁移浸润并造成肝脏损伤。

To investigate the important roles of chemokines and chemokine receptors in regulating the migration of effect cells in graft versus-host disease （GVHD）, a murine GVHD model to analysis chemokine and chemokine receptor expression in the liver and the allo-CD8^＋ T cell was used. By means of flow cytometry analysis （FACS） and real time PCR, we found that liver of GVHD expressed high level of interferon inducible protein 10 （IP-10）, interferon-induclble T cell alpha chemoattractant （ITAC）, monokine induced by IFN-）＇ （MIG）, and macrophage inflammatory protein （MIP）-1α/β. The infiltrated allo-CD8^＋ T cells, accordingly, expressed high CXC chemokine receptor 3 （CXCR3） and CC chemokine receptor 5（CCR5）. The number of allo-CD8^＋ T cells in liver increased along with the up regulated expression of chemokines, so the relative specific relation of the allo-CD8^＋ T cells and the target tissue of GVHD encouraged the migration and infiltration of allo-CD8 ^＋ T cells and caused tissue damage.