The brain barriers establish compartments in the central nervous system (CNS) that significantly differ in their communication with the peripheral immune system. In this function they strictly control T-cell entry into the CNS. T cells can reach the CNS by either crossing the endothelial blood–brain barrier (BBB) or the epithelial blood-cerebrospinal fluid barrier (BCSFB) of the choroid plexus (ChP). Analysis of the cellular and molecular mechanisms involved in the migration of different human CD4+ T-cell subsets across the BBB versus the BCSFB. Human in vitro models of the BBB and BCSFB were employed to study the migration of circulating and CNS-entry experienced CD4+ T helper cell subsets (Th1, Th1*, Th2, Th17) across the BBB and BCSFB under inflammatory and non-inflammatory conditions in vitro. While under non-inflammatory conditions Th1* and Th1 cells preferentially crossed the BBB, under inflammatory conditions the migration rate of all Th subsets across the BBB was comparable. The migration of all Th subsets across the BCSFB from the same donor was 10- to 20-fold lower when compared to their migration across the BBB. Interestingly, Th17 cells preferentially crossed the BCSFB under both, non-inflamed and inflamed conditions. Barrier-crossing experienced Th cells sorted from CSF of MS patients showed migratory characteristics indistinguishable from those of circulating Th cells of healthy donors. All Th cell subsets could additionally cross the BCSFB from the CSF to ChP stroma side. T-cell migration across the BCSFB involved epithelial ICAM-1 irrespective of the direction of migration. Our observations underscore that different Th subsets may use different anatomical routes to enter the CNS during immune surveillance versus neuroinflammation with the BCSFB establishing a tighter barrier for T-cell entry into the CNS compared to the BBB. In addition, CNS-entry experienced Th cell subsets isolated from the CSF of MS patients do not show an increased ability to cross the brain barriers when compared to circulating Th cell subsets from healthy donors underscoring the active role of the brain barriers in controlling T-cell entry into the CNS. Also we identify ICAM-1 to mediate T cell migration across the BCSFB.

中文翻译：

---

人 CD4+ T 细胞亚群在体外穿过内皮和上皮脑屏障的能力不同

脑屏障在中枢神经系统 (CNS) 中建立隔室，这些隔室在与外周免疫系统的交流方面存在显着差异。在这个功能中，它们严格控制 T 细胞进入中枢神经系统。T 细胞可以通过内皮血脑屏障 (BBB) 或脉络丛 (ChP) 的上皮血脑脊液屏障 (BCSFB) 到达 CNS。分析涉及不同人类 CD4+ T 细胞亚群跨 BBB 与 BCSFB 迁移的细胞和分子机制。BBB 和 BCSFB 的人体外模型用于研究在炎症和非炎症条件下循环和中枢神经系统进入经历的 CD4+ T 辅助细胞亚群（Th1、Th1*、Th2、Th17）在 BBB 和 BCSFB 中的迁移。体外。虽然在非炎症条件下 Th1* 和 Th1 细胞优先穿过 BBB，但在炎症条件下，所有 Th 亚群穿过 BBB 的迁移率相当。与跨 BBB 的迁移相比，来自同一供体的所有 Th 子集跨 BCSFB 的迁移低 10 到 20 倍。有趣的是，在非炎症和炎症条件下，Th17 细胞优先穿过 BCSFB。从 MS 患者的 CSF 中分选的屏障交叉经历的 Th 细胞显示出与健康供体循环 Th 细胞的迁移特征无法区分的迁移特征。所有 Th 细胞亚群还可以从 CSF 到 ChP 基质侧穿过 BCSFB。无论迁移方向如何，T 细胞跨越 BCSFB 的迁移都涉及上皮 ICAM-1。我们的观察结果强调，与 BBB 相比，BCSFB 为 T 细胞进入 CNS 建立了更紧密的屏障，在免疫监视与神经炎症期间，不同的 Th 亚群可能使用不同的解剖途径进入 CNS。此外，与来自健康供体的循环 Th 细胞亚群相比，从 MS 患者的脑脊液中分离出的中枢神经系统进入经历的 Th 细胞亚群没有表现出增强的穿越脑屏障的能力，这强调了脑屏障在控制 T-细胞进入中枢神经系统。我们还确定了 ICAM-1 来介导 T 细胞在 BCSFB 中的迁移。与来自健康供体的循环 Th 细胞亚群相比，从 MS 患者的 CSF 中分离出的 CNS 进入经历的 Th 细胞亚群没有表现出增强的穿越脑屏障的能力，这强调了脑屏障在控制 T 细胞进入的积极作用中枢神经系统。我们还确定了 ICAM-1 来介导 T 细胞在 BCSFB 中的迁移。与来自健康供体的循环 Th 细胞亚群相比，从 MS 患者的 CSF 中分离出的 CNS 进入经历的 Th 细胞亚群没有表现出增强的穿越脑屏障的能力，这强调了脑屏障在控制 T 细胞进入的积极作用中枢神经系统。我们还确定了 ICAM-1 来介导 T 细胞在 BCSFB 中的迁移。