Normal adult ramified microglia separated from other central nervous system macrophages by flow cytometric sorting. Phenotypic differences defined and direct ex vivo antigen presentation to myelin basic protein-reactive CD4+ T cells compared.
Normal adult ramified microglia separated from other central nervous system macrophages by flow cytometric sorting. Phenotypic differences defined and direct ex vivo antigen presentation to myelin basic protein-reactive CD4+ T cells compared.
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DOI：
10.4049/jimmunol.154.9.4309
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发表时间：
1995-05
影响因子：
4.4
通讯作者：
A. L. Ford;A. Goodsall;W. Hickey;J. Sedgwick
中科院分区：
文献类型：
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作者：
A. L. Ford;A. Goodsall;W. Hickey;J. Sedgwick
成人中枢神经系统(CNS)中的分支小胶质细胞是主要的胶质细胞成分，在炎症事件或神经元损伤时上调MHC I和II类的表达。在正常的中枢神经系统中，部分细胞也表达MHC-II类分子。小胶质细胞作为CD4+T细胞渗入中枢神经系统的APC的作用尚不明确。在这项研究中，利用CD45同源基因大鼠的辐射骨髓嵌合体，表型CD45lowCD11b/c+被证明能够识别中枢神经系统中特异的小胶质细胞。通过流式细胞仪分选，直接从成人中枢神经系统获得了高纯度的小胶质细胞和非小胶质但与中枢神经系统相关的巨噬细胞(CD45HighCD11b/c+)。形态上，新鲜分离的小胶质细胞与其他中枢神经系统巨噬细胞截然不同。在从正常中枢恢复的两个群体中，少数CD45HighCD11b/c+过渡性巨噬细胞群体，而不是小胶质细胞，是实验性自身免疫性脑脊髓炎诱导的CD4+髓鞘碱性蛋白(MBP)反应性T细胞的有效APC。CD45HighCD11b/c+CNS巨噬细胞也刺激MBP反应性T细胞，而不向培养中添加MBP，提示存在内源性抗原。这是第一次对小胶质细胞和其他中枢神经系统巨噬细胞直接从中枢神经系统分析APC能力的研究，消除了两个群体之间的实质性交叉污染。这些群体在APC功能方面的异质性被清楚地证明。目前尚无证据表明成年中枢神经系统小胶质细胞具有与CD4+T细胞相互作用并刺激其增殖或分泌IL-2的能力。
Ramified microglia in the adult central nervous system (CNS) are the principal glial element up-regulating MHC class I and II expression in response to inflammatory events or neuronal damage. A proportion of these cells also express MHC class II constitutively in the normal CNS. The role of microglia as APCs for CD4+ T cells extravasating into the CNS remains undefined. In this study, using irradiation bone marrow chimeras in CD45-congenic rats, the phenotype CD45lowCD11b/c+ is shown to identify microglial cells specifically within the CNS. Highly purified populations of microglia and nonmicroglial but CNS-associated macrophages (CD45highCD11b/c+) have been obtained directly from the adult CNS, by using flow cytometric sorting. Morphologically, freshly isolated microglia vs other CNS macrophages are quite distinct. Of the two populations recovered from the normal CNS, it is the minority CD45highCD11b/c+ transitional macrophage population, and not microglia, that is the effective APC for experimental autoimmune encephalomyelitis-inducing CD4+ myelin basic protein (MBP)-reactive T cells. CD45highCD11b/c+ CNS macrophages also stimulate MBP-reactive T cells without addition of MBP to culture, suggesting presentation of endogenous Ag. This is the first study in which microglia vs other CNS macrophages have been analyzed for APC ability directly from the CNS, with substantial cross-contamination between the two populations eliminated. The heterogeneity of these populations in terms of APC function is clearly demonstrated. Evidence is still lacking that adult CNS microglia have the capacity to interact with and stimulate CD4+ T cells to proliferate or secrete IL-2.