再生障碍性贫血患者T细胞表面VLA-4和CX3CR1的表达  

Expression and significance of VLA-4 and CX3CR1 in aplastic anemia

作　　者：任娟[1] 甄军辉[2] 孙建芝[1] 马士卉[1] 孙琳[1] 王旭平[3] 王文[1] 于媛[1] 曲迅[4] 张茂宏[1] 徐从高[1] 彭军[1] 

机构地区：[1]山东大学齐鲁医院血液科,济南250012 [2]山东大学齐鲁医院病理科 [3]山东大学齐鲁医院心血管重构与功能研究重点实验室 [4]山东大学齐鲁医院临床基础研究所

出　　处：《临床血液学杂志》2011年第1期1-5,共5页Journal of Clinical Hematology

基　　金：山东省优秀中青年科学家奖励基金(No:2007BS03049)

摘　　要：目的:探讨获得性再生障碍性贫血(AA)患者T细胞表面VLA-4、CX3CR1的表达在AA发病机制中的作用。方法:①流式细胞术分析46例AA患者(20例重型AA,26例非重型AA)骨髓和外周血中T淋巴细胞亚群的变化以及VLA-4、CX3CR1在T淋巴细胞亚群上的表达。②ELISA方法测定其骨髓和外周血浆中VCAM-1(VLA-4的配体)、Fractalkine(CX3CR1的配体)的含量。结果:①AA患者外周血中CD3+细胞比例基本正常(P>0.05),CD8+细胞比例明显上升,CD4+细胞比例明显下降(P<0.01);骨髓中CD3+、CD8+细胞比例均明显升高(P<0.01),CD4+细胞比例减低仅在重型AA患者中差异有统计学意义(P<0.05)。②AA患者骨髓和外周血T细胞亚群表面VLA-4的表达与对照组比较均差异无统计学意义(均P>0.05)。然而患者骨髓和外周血中CD3+/CX3CR1+细胞、CD3+/CD4+/CX3CR1+细胞以及CD3+/CD8+/CX3CR1+细胞比例均升高(P<0.05),尤其CD3+/CD8+/CX3CR1+细胞比例升高更为显著(P<0.01)。③AA患者骨髓和外周血浆中VCAM-1水平与对照组比较均无明显变化(P>0.05)。而Fractalkine水平在重型和非重型AA患者骨髓中以及重型AA患者外周血浆中均升高(P<0.05)。结论:获得性AA作为一种T细胞介导的免疫性疾病,存在T细胞亚群失衡。T细胞通过高表达CX3CR1,与Fractalkine相互作用,从外周血迁移到骨髓,并在骨髓中积聚导致造血干/祖细胞的破坏。Objective：To investigate the contribution of the expression of VLA-4 and CX3CR1 on T cells surface to the pathogenesis of acquired aplastic anemia （AA）.Method：①The percentage of T cell subsets and the expression of VLA-4 and CX3CR1 on T cells from peripheral blood and bone marrow were analyzed by flow cytometry in 46 AA patients （20 with severe aplastic anemia and 26 with non-severe aplastic anemia）. ②The levels of VCAM-1 （ligand of VLA-4） and Fractalkine （ligand of CX3CR1） were investigated in blood and bone marrow from AA patients and controls by Enzyme-linked immunosorbent assay.Result：①In peripheral blood,there was no significant difference of the percentage of CD3＋ cells （P0.05）. But increased CD8＋ cells and reduced CD4＋ cells were found in AA patients （P0.01）. In bone marrow,both the percentage of CD3＋ cells and CD8＋ cells were increased in AA patients （P0.01）. And significantly lower percentage of CD4＋ cells was only found in SAA patients （P0.05）. ②Both in blood and bone marrow,there was no statistically significant difference of the expression of VLA-4 on T cell subsets （P0.05）. However,the percentage of CD3＋/CX3CR1＋ cells、CD3＋/CD4＋/CX3CR1＋ cells,and especially CD3＋/CD8＋/CX3CR1＋ cells were increased in AA patients compared with controls （P0.05）. ③ There were no significant difference of the levels of VCAM-1 in blood or bone marrow plasma between AA patients and controls （P0.05）,but the plasma levels of Fractalkine were significantly higher in SAA patients＇ blood and all the patients＇ bone marrow （P0.05）.Conclusion：Acquired AA is a T-cell-media-ted immune disease,and presents abnormal T cell subsets. T cells appear to relocate from peripheral blood and accumulate in bone marrow to destruct hematopoietic stem and progenitor cells,probably due to elevated expression of surface CX3CR1 interacting with Fractalkine.

关 键 词：贫血 再生障碍性 CX3CR1 VLA-4 T细胞亚群 

分 类 号：R556[医药卫生—血液循环系统疾病]