Disproportionate recruitment of CD8+ T cells into the central nervous system by professional antigen-presenting cells
Disproportionate recruitment of CD8+ T cells into the central nervous system by professional antigen-presenting cells
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DOI：
10.1016/s0002-9440(10)65294-7
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发表时间：
1999-02-01
影响因子：
6
通讯作者：
Lo, D
中科院分区：
文献类型：
--
作者：
Carson, MJ;Reilly, CR;Lo, D
不适当的免疫反应，被认为是加剧或甚至启动几种类型的中枢神经系统（CNS）神经病理学，可能是由CNS或免疫系统的失败引起的。抗原呈递细胞（APC）功能的不适当表现在CNS炎症和病理学中的作用程度仍在争论中。因此，我们将呈递非CNS抗原的专职APC（树突状细胞）注射到CNS中时所引发的反应进行了表征。这些树突状细胞表达多种T细胞趋化因子，但仅在抗原存在下，白细胞才在脑室、脑膜、蛛网膜下腔和注射部位积聚。在中枢神经系统实质内，注射的树突状细胞优先迁移到白色物质束，但只有一小部分招募的白细胞进入中枢神经系统实质，然后只在白色物质束。虽然T细胞募集是抗原特异性的，因此在这里使用的模型中由CD 4（+）T细胞介导，但CD 8（+）T细胞的数量等于或大于CD 4（+）T细胞的数量。招募的T细胞中很少有表达活化标志物（CD 25和VLA-4）的，并且那些主要在脑膜、注射部位、心室和血管周围空间中，但不在实质中。这些结果表明：1）CNS调节细胞组成和应答T细胞群的活化状态，2）髓鞘限制性炎症不需要由髓鞘特异性抗原引发。
Inappropriate immune responses, thought to exacerbate or even to initiate several types of central nervous system (CNS) neuropathology, could arise from failures by either the CNS or the immune system. The extent that the inappropriate appearance of antigen-presenting cell (APC) function contributes to CNS inflammation and pathology is still under debate. Therefore, we characterized the response initiated when professional APCs (dendritic cells) presenting non-CNS antigens were injected into the CNS, These dendritic cells expressed numerous T-cell chemokines, but only in the presence of antigen did leukocytes accumulate in the ventricles, meninges, subarachnoid spaces, and injection site. Within the CNS parenchyma, the injected dendritic cells migrated preferentially into the white matter tracts, yet only a small percentage of the recruited leukocytes entered the CNS parenchyma, and then only in the white matter tracts. Although T-cell recruitment was antigen specific and thus mediated by CD4(+) T cells in the models used here, CD8(+) T cells accumulated in numbers equal to or greater than that of CD4(+) T cells. Few of the recruited T cells expressed activation markers (CD25 and VLA-4), and those that did were primarily in the meninges, injection site, ventricles, and perivascular spaces but not in the parenchyma. These results indicate that 1) the CNS modulates the cellular composition and activation states of responding T-cell populations and that 2) myelin-restricted inflammation need not be initiated by a myelin-specific antigen.