Defining antigen-dependent stages of T cell migration from the blood to the central nervous system parenchyma
Defining antigen-dependent stages of T cell migration from the blood to the central nervous system parenchyma
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DOI：
10.1002/eji.200425864
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发表时间：
2005-04-01
影响因子：
5.4
通讯作者：
Russell, JH
中科院分区：
文献类型：
--
作者：
Archambault, AS;Sim, J;Russell, JH
在实验性自身免疫性脑脊髓炎(EAE)中，静脉转移活化的CD4(+)髓鞘特异性T细胞足以诱发疾病。被转移的T细胞通过跨越血脑屏障(BBB)血管内皮细胞进入血管周围空间，然后跨越由星形胶质细胞和小胶质细胞组成的神经胶质界限，从而进入中枢神经系统实质。从中枢神经系统组织分离的细胞的流式细胞术分析不能区分不同迁移阶段的T细胞群。在这项研究中，我们使用GK1.5(抗CD4)治疗和免疫组织化学相结合的方法来区分与血管系统相关的T细胞群、迁移到血管周围间隙的T细胞和实质中的T细胞。当T细胞被招募到中枢神经系统实质时，我们也重新评估了它们的抗原特异性要求。活化的髓鞘特异性T细胞在移植后至少24小时限制在中枢神经系统的血管内。受体上MHC II类分子的表达是细胞通过中枢神经系统血管内皮细胞所必需的。此外，ConA刺激的或非CNS特异性(卵清蛋白特异性)T细胞不能迁移到血管周围空间，只有在与髓鞘特异性T细胞共转移时才进入CNS实质。我们的结果表明，如果没有中枢神经系统抗原特异性信号，Th1细胞不能聚集在血管周围(蛛网膜下腔，Virchow-Robbins)空间。
In experimental autoimmune encephalomyelitis (EAE), intravenous transfer of activated CD4(+) myelin-specific T cells is sufficient to induce disease. Transferred T cells access the CNS parenchyma by trafficking across the blood brain barrier (BBB) vascular endothelium into the perivascular space, and then across the glial limitans that is made up of astrocytes and microglia. Flow cytometry analysis of cells isolated from CNS tissue does not distinguish between T cell populations at the various stages of migration. In this study, we have used GK1.5 (anti-CD4) treatment along with immunohistochemistry to distinguish between populations of T cells that are associated with the vasculature, T cells that have migrated into the perivascular space, and T cells in the parenchyma. We have also re-evaluated antigen specificity requirements of T cells as they are recruited to the CNS parenchyma. Activated myelin-specific T cells are restricted to the CNS vasculature for at least 24 h post transfer. MHC class II expression on the recipient is required for cells to traffic across the CNS vascular endothelium. Further, Con A-stimulated or non-CNS-specific (ovalbumin-specific) T cells fail to migrate into the perivascular space, and only enter the CNS parenchyma when co-transferred with myelin-specific T cells. Our results indicate that Th1 populations cannot accumulate in the perivascular (subarachnoid, Virchow-Robbins) space without a CNS antigen-specific signal.