Localizing central nervous system immune surveillance: meningeal antigen-presenting cells activate T cells during experimental autoimmune encephalomyelitis.
Localizing central nervous system immune surveillance: meningeal antigen-presenting cells activate T cells during experimental autoimmune encephalomyelitis.
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DOI：
10.1002/ana.21379
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发表时间：
2009-04
影响因子：
11.2
通讯作者：
Khoury, Samia J.
中科院分区：
文献类型：
--
作者：
Kivisakk, Pia;Imitola, Jaime;Rasmussen, Stine;Elyaman, Wassim;Zhu, Bing;Ransohoff, Richard M.;Khoury, Samia J.
实验性自身免疫性脑脊髓炎 (EAE) 中神经系统体征的出现与 CNS 中 T 细胞的浸润和重新激活密切相关。然而，导致中枢神经系统中 T 细胞重新激活的初始 T 细胞-APC 相互作用的解剖学定位仍不清楚。我们假设激活的 CD4+ T 细胞可以直接进入蛛网膜下腔，并在遇到该区室中的同源抗原时重新激活。用 MOG35-55 免疫 C57Bl/6 小鼠，并使用流式细胞术、软脑膜整体制备物的共聚焦显微镜、软脑膜外植体的延时显微镜和体外增殖测定来研究蛛网膜下腔中 CD4+ T 细胞和 MHC II+ APC 之间的相互作用。在 EAE 病程早期，在脊髓实质中检测到 CD4+ T 细胞之前，极化产生 Th1/Th17 细胞因子的 CD4+ T 细胞在蛛网膜下腔积聚。此时，软脑膜而非实质 CD4+ T 细胞掺入了 BrdU，表明 CD4+ T 细胞在蛛网膜下腔局部增殖。延时显微镜表明，这些 CD4+ T 细胞主动扫描组织并与局部 MHC II 类阳性 APC 相互作用，导致 CD4+ T 细胞与 MHC II 类阳性 APC 之间产生持久的相互作用，提示存在免疫突触。这些结果支持中枢神经系统的免疫监视涉及蛛网膜下腔的概念，并表明软脑膜在 EAE 发生中发挥重要作用。
The onset of neurological signs in experimental autoimmune encephalomyelitis (EAE) is tightly associated with infiltration and reactivation of T cells in the CNS. The anatomical localization of the initial T cell-APC interactions leading to reactivation of T cells in the CNS is, however, still unclear. We hypothesized that activated CD4+ T cells gain direct access to the subarachnoid space and become reactivated upon encounter with cognate antigen in this compartment. C57Bl/6 mice were immunized with MOG35-55 and interactions between CD4+ T cells and MHC class II+ APCs in the subarachnoid space were investigated using flow cytometry, confocal microscopy of leptomeningeal whole-mount preparations, time-lapse microscopy of leptomeningeal explants, and in vitro proliferation assays. CD4+ T cells, polarized to produce Th1/Th17 cytokines, accumulated in the subarachnoid space early during the course of EAE, before CD4+ T cells were detected in the spinal cord parenchyma. At this time point, leptomeningeal, but not parenchymal CD4+ T cells incorporated BrdU, indicating local proliferation of CD4+ T cells in the subarachnoid space. Time lapse microscopy indicated that these CD4+ T cells actively scanned the tissue and interacted with local MHC class II positive APCs, resulting in long-lasting interactions between CD4+ T cells and MHC class II positive APCs, suggestive of immunological synapses. These results support the concept that immune surveillance of the CNS involves the subarachnoid space and indicate that the leptomeninges play an important role in EAE initiation.
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影响因子：
56.9
作者：
Butcher, EC;Picker, LJ
通讯作者：
Picker, LJ
影响因子：
6.4
作者：
Hickey, William F.
通讯作者：
Hickey, William F.
影响因子：
158.5
作者：
Hsich, G;Kinney, K;Harrington, MG
通讯作者：
Harrington, MG
影响因子：
56.9
作者：
Lee, KH;Holdorf, AD;Shaw, AS
通讯作者：
Shaw, AS
影响因子：
82.9
作者：
Greter, M;Heppner, FL;Becher, B
通讯作者：
Becher, B