Department of Neurobiology, Taishan Medical College, Taian, Shandong Province, People's Republic of China.
PLoS One. 2009 Nov 17;4(11):e7869. doi: 10.1371/journal.pone.0007869.
The central nervous system (CNS) is generally regarded as a site of immune privilege, whether the antigen presenting cells (APCs) are involved in the immune homeostasis of the CNS is largely unknown. Microglia and DCs are major APCs in physiological and pathological conditions, respectively. In this work, primary microglia and microglia-like cells obtained by co-culturing mature dendritic cells with CNS endothelial cells in vitro were functional evaluated. We found that microglia not only cannot prime CD4 T cells but also inhibit mature DCs (maDCs) initiated CD4 T cells proliferation. More importantly, endothelia from the CNS can differentiate maDCs into microglia-like cells (MLCs), which possess similar phenotype and immune inhibitory function as microglia. Soluble factors including NO lie behind the suppression of CD4 T cell proliferation induced by both microglia and MLCs. All the data indicate that under physiological conditions, microglia play important roles in maintaining immune homeostasis of the CNS, whereas in a pathological situation, the infiltrated DCs can be educated by the local microenvironment and differentiate into MLCs with inhibitory function.
中枢神经系统(CNS)通常被认为是免疫特权的部位,抗原呈递细胞(APCs)是否参与 CNS 的免疫稳态在很大程度上是未知的。小胶质细胞和 DCs 分别是生理和病理条件下的主要 APCs。在这项工作中,我们对原代小胶质细胞和通过与 CNS 内皮细胞共培养成熟树突状细胞体外获得的小胶质样细胞进行了功能评估。我们发现小胶质细胞不仅不能刺激 CD4 T 细胞,而且还抑制成熟树突状细胞(maDCs)启动的 CD4 T 细胞增殖。更重要的是,来自 CNS 的内皮细胞可以将 maDCs 分化为小胶质样细胞(MLCs),其具有与小胶质细胞相似的表型和免疫抑制功能。包括 NO 在内的可溶性因子是小胶质细胞和 MLCs 诱导的 CD4 T 细胞增殖抑制的背后原因。所有数据表明,在生理条件下,小胶质细胞在维持 CNS 的免疫稳态中发挥重要作用,而在病理情况下,浸润的 DCs 可以被局部微环境所诱导,并分化为具有抑制功能的 MLCs。