MICROGLIAL INVOLVEMENT IN EXPERIMENTAL AUTOIMMUNE INFLAMMATION OF THE CENTRAL AND PERIPHERAL NERVOUS-SYSTEM

MICROGLIAL INVOLVEMENT IN EXPERIMENTAL AUTOIMMUNE INFLAMMATION OF THE CENTRAL AND PERIPHERAL NERVOUS-SYSTEM
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DOI:
10.1002/glia.440070110
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发表时间:
1993-01-01
期刊:
影响因子:
6.2
通讯作者:
KREUTZBERG, GW
KREUTZBERG, GW
中科院分区:
医学1区
文献类型:
--
作者:
GEHRMANN, J;GOLD, R;KREUTZBERG, GW

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小胶质细胞在整个神经系统中形成潜在的抗原呈递细胞网络。最近取得了很大进展,以更好地了解其免疫特性。本研究探讨了它们的激活在2个模型的T细胞介导的自身免疫性炎症的神经系统,实验性自身免疫性脑脊髓炎(EAE)和其周边的对应物,实验性自身免疫性神经炎(EAN),诱导转移的抗原特异性T细胞系。在这两种模型中,小胶质细胞活化发生在疾病的早期阶段。活化的小胶质细胞显示MHC I类和II类抗原的表达增加。在EAE超微结构分析显示,MHC抗原表达是显着的血管周围的小胶质细胞,这表明该细胞群可能是重要的抗原呈递在一个网站接近血脑屏障。与EAE相反,EAN中的小胶质细胞反应发生在远离周围神经中的炎症反应的部位,不仅在脊髓中,而且在下脑干中初级感觉神经元的终末投射野中。EAN中的这种早期小胶质细胞活化表明,在外周炎症后,快速和远程信号传导机制可以起作用。免疫电镜显示,激活的小胶质细胞也参与了脊髓运动神经元在自身免疫反应的突触传入。小胶质细胞在神经系统的实验性自身免疫性炎症中的快速参与进一步指出了它们作为中枢神经系统的主要内在免疫效应细胞群体的作用。
Microglial cells form a network of potential antigen presenting cells throughout the nervous system. Much progress has recently been made towards a better understanding of their immunological properties. This study examines their activation in 2 models of T cell-mediated autoimmune inflammation of the nervous system, experimental autoimmune encephalomyelitis (EAE) and its peripheral counterpart, experimental autoimmune neuritis (EAN), induced by the transfer of antigen-specific T cell lines. In both models microglial activation occurs at early stages of the disease. Activated microglial cells show an increased expression of MHC class I and II antigens. In EAE ultrastructural analysis revealed that MHC antigen expression is pronounced on perivascular microglial cells, suggesting this cell population may be important for antigen presentation at a site close to the blood-brain barrier. In contrast to EAE, the microglial reaction in EAN occurs at sites remote from the inflammatory response in the peripheral nerve, not only in the spinal cord but also in the terminal projection fields of primary sensory neurons in the lower brainstem. This early microglial activation in EAN suggests that a rapid and remote signaling mechanism can operate following peripheral inflammation. Immuno-electron microscopy revealed that activated microglial cells are also involved in the synaptic deafferentation of spinal cord motoneurons during autoimmune reactions. The rapid involvement of microglial cells in experimental autoimmune inflammation of the nervous system further points to their role as the main intrinsic immuneffector cell population of the central nervous system.