Distribution of the Immune Inhibitory Molecules CD200 and CD200R in the Normal Central Nervous System and Multiple Sclerosis Lesions Suggests Neuron-Glia and Glia-Glia Interactions
Distribution of the Immune Inhibitory Molecules CD200 and CD200R in the Normal Central Nervous System and Multiple Sclerosis Lesions Suggests Neuron-Glia and Glia-Glia Interactions
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DOI：
10.1097/nen.0b013e3181964113
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发表时间：
2009-02-01
影响因子：
3.2
通讯作者：
Huitinga, Inge
中科院分区：
文献类型：
--
作者：
Koning, Nathalie;Swaab, Dick F.;Huitinga, Inge
CD 200是一种膜糖蛋白，通过其受体抑制免疫活性，CD 200-CD 200 R相互作用最近被认为有助于中枢神经系统（CNS）的“免疫特权”状态。这些相互作用发生的机制尚未得到很好的理解，部分原因是关于CD 200和CD 200 R在CNS中分布的详细信息有限。在这里，我们使用免疫组织化学来表征这些分子在多发性硬化（MS）病变和对照中的不同解剖和细胞分布。CD 200在包括大脑皮质、海马、纹状体、小脑和脊髓的灰质区域中强烈表达，其中神经元呈现免疫阳性。在少突胶质细胞中也检测到CD 200表达，但在星形胶质细胞或小胶质细胞中未检测到。在MS患者的CNS样本中，在慢性活动性斑块中心的反应性星形胶质细胞上还观察到CD 200表达，尽管我们先前发现MS病变中CD 200表达总体降低。与CD 200相比，CD 200 R的免疫定位模式非常明显，在血管周围巨噬细胞的灰色和白色物质中均显示高表达。我们还使用流式细胞术发现，人原代小胶质细胞表达低水平的CD 200 R。这些数据表明，CD 200介导的免疫抑制可能不仅通过神经元-小胶质细胞相互作用发生，而且通过胶质细胞-胶质细胞相互作用发生，特别是在需要恢复免疫抑制环境的炎症条件下;这可能是由于反应性星形胶质细胞上CD 200表达增加而发生的。
CD200 is a membrane glycoprotein that suppresses immune activity via its receptor, CD200R CD200-CD200R interactions have recently been considered to contribute to the "immune privileged" status of the central nervous system (CNS). The mechanisms by which these interactions take place are not well understood in part because there is limited detailed information on the distribution of CD200 and CD200R in the CNS. Here, we used immunohistochemistry to characterize the distinct anatomical and cellular distribution of these molecules in multiple sclerosis (MS) lesions and controls. CD200 was robustly expressed in gray matter areas including the cerebral cortex, hippocampus, striatum, cerebellum, and spinal cord, where neurons appeared immunopositive. CD200 expression was also detected in oligodendrocytes, but not in astrocytes or microglia. In CNS samples from MS patients, CD200 expression was additionally observed on reactive astrocytes in chronic active plaque centers, despite our previous finding of an overall decrease of CD200 expression in MS lesions. In contrast to CD200, the immunolocalization pattern of CD200R was very distinct, showing high expression on perivascular macrophages in both gray and white matter, Using flow cytometry, we also found that human primary microglia express low levels of CD200R. These data suggest that CD200-mediated immune suppression may occur not only via neuron-microglia interactions, but also via glia-glia interactions, especially in inflammatory conditions in which an immune-suppressive environment needs to be restored; this may occur as a result of increased CD200 expression on reactive astrocytes.