CD4 microglial expression correlates with spontaneous clinical improvement in the acute Lewis rat EAE model
CD4 microglial expression correlates with spontaneous clinical improvement in the acute Lewis rat EAE model
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DOI：
10.1016/j.jneuroim.2009.01.026
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发表时间：
2009-04-30
影响因子：
3.3
通讯作者：
Castellano, Bernardo
中科院分区：
文献类型：
--
作者：
Almolda, Beatriz;Costa, Manuela;Castellano, Bernardo
CD4是一种普遍表达在T辅助淋巴细胞表面的分子，在抗原呈递过程中具有公认的关键作用，在单核细胞和巨噬细胞中也有报道，尽管它在这些细胞中的作用尚不清楚。本研究的目的是分析实验性自身免疫性脑脊髓炎(EAE)中涉及强效获得性免疫成分的实验条件是否能够诱导小胶质细胞/巨噬细胞群中CD4的表达。用髓鞘碱性蛋白(MBP)免疫的雌性Lewis大鼠，根据临床评分，在EAE过程中的不同时相进行检测。用流式细胞术检测脊髓CD11b、CD4和CD45的表达，用组织化学方法检测NDPase的表达，用免疫组织化学方法检测ED2、IBA1、CD45和CD4的表达。流式细胞仪分析显示，EAE可诱导巨噬细胞(CD11b+/CD45(高))和小胶质细胞(CD11b+/CD45(中)和CD11b+/CD45(低)表型)表达CD4。值得注意的是，在恢复期发现了小胶质细胞CD4的表达，并一直保持到诱导后40天。免疫标记切片显示，在恢复期和恢复期，小胶质细胞中有CD4的表达，形态呈分枝状。综上所述，我们的结果表明，在EAE模型中，血管周围细胞、小胶质细胞和巨噬细胞在疾病过程中表现出与症状密切相关的不同动态，而小胶质细胞在恢复期有趣地表达CD4，提示小胶质细胞CD4表达在免疫应答的解决中起作用。(C)2009爱思唯尔B.V.保留所有权利。
CD4 is a molecule commonly expressed on the surface of T-helper lymphocytes with a recognized critical role in the antigen presentation process that has also been reported in monocytes and macrophages, although its role in these cells remains unknown. The objective of the present study was to analyze whether experimental conditions involving a potent acquired immune component, as occurs in experimental autoimmune encephalomyelitis (EAE), are able to induce CD4 expression in the population of microglia/macrophages. Myelin Basic Protein (MBP) immunized female Lewis rats, were examined at different phases during the course of EAE according to their clinical score. Spinal cords were analyzed by flow cytometry for CD11b, CD4 and CD45, by histochemistry for NDPase and by immunohistochemistry for ED2, Iba1, CD45 and CD4. Flow cytometry analysis showed that EAE induced CD4 expression in macrophages (CD11b+/CD45(high)) and microglia (in both CD11b+/CD45(intermediate) and CD11b+/CD45(low) phenotypes). Noticeably, microglial CD4 expression was found during the recovery phase and was maintained until 40 days post-induction. In agreement, immunolabelled sections revealed CD4 expression in microglial cells with ramified morphology during the recovery and post-recovery phases. In conclusion, our results indicate that, in this EAE model, perivascular cells, microglia and macrophages showed different dynamics during the course of the disease in close relation with symptomatology and that microglial cells expressed CD4 interestingly during the recovery phase, suggesting a role of microglial CD4 expression in the resolution of the immune response. (C) 2009 Elsevier B.V. All rights reserved.