Involvement of CCR5 in the passage of Th1-type cells across the blood-retina barrier in experimental autoimmune uveitis
Involvement of CCR5 in the passage of Th1-type cells across the blood-retina barrier in experimental autoimmune uveitis
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DOI：
10.1189/jlb.0305130
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发表时间：
2006-03-01
影响因子：
5.5
通讯作者：
Forrester, John V.
中科院分区：
文献类型：
--
作者：
Crane, Isabel J.;Xu, Heping;Forrester, John V.
虽然募集T辅助细胞I型（Th 1）/Th 2细胞进入外周组织是必不可少的炎症和宿主对感染的反应，交通信号，使不同的定位Th 1/Th 2细胞是不清楚的。我们已经确定了CC趋化因子受体5（CCR 5）在此使用实验性自身免疫性葡萄膜炎（EAU）作为模型系统的作用。在EAU中，Th 1样细胞优先通过血-视网膜屏障进入视网膜，部分原因是这些细胞上粘附分子P-选择素糖蛋白配体I和淋巴细胞功能相关抗原-1的表达。浸润视网膜的CD 3 + T细胞也表达趋化因子受体CCR 5和CCR 5配体、巨噬细胞炎性蛋白-1 α（MIP-1 α）、MIP-1 β和活化调节的正常T表达和分泌（RANTES），在EAU峰值时在视网膜中强烈表达。体外极化的Th 1样细胞表达高水平的CCR 5。通过在疾病早期阶段在体内真实的时间内追踪过继转移后的这些CCR 5（+）细胞来检查它们的运输。在转移之前用针对CCR 5的抗体处理细胞导致它们向视网膜中的浸润减少。然而，滚动速度，滚动效率，和粘附的细胞视网膜内皮细胞没有减少。CCR 5对于Th 1细胞的募集显然是重要的，并且本研究首次在体内证明了CCR 5可能在跨内皮迁移的水平上起作用，而不是在内皮上滚动的早期阶段起作用。
Although the recruitment of T helper cell type I (Th1)/Th2 cells into peripheral tissues is essential for inflammation and the host response to infection, the traffic signals that enable the distinct positioning of Th1/Th2 cells are unclear. We have determined the role of CC chemokine receptor 5 (CCR5) in this using experimental antoimmune uveitis (EAU) as a model system. In EAU, Th1-like cells are preferentially recruited into the retina across the blood-retina barrier, partly as a result of expression of the adhesion molecules P-selectin glycoprotein ligand I and lymphocyte function-associated antigen-1 on these cells. CD3+ T cells, infiltrating the retina, also expressed the chemokine receptor CCR5, and CCR5 ligands, macrophage-inflammatory protein-1 alpha (MIP-1 alpha), MIP-1 beta, and regulated on activation, normal T expressed and secreted (RANTES), were strongly expressed in the retina at peak EAU. Th1-like cells, polarized in vitro, expressed high levels of CCR5. The trafficking of these CCR5(+) cells was examined by tracking them after adoptive transfer in real time in vivo at an early disease stage using scanning laser ophthalmoscopy. Treatment of the cells with antibody against CCR5 prior to transfer resulted in a reduction in their infiltration into the retina. However, rolling velocity, rolling efficiency, and adherence of the cells to retinal endothelium were not reduced. CCR5 is clearly important for Th1 cell recruitment, and this study demonstrates for the first time in vivo that CCR5 may act at the level of transendothelial migration rather than at the earlier stage of rolling on the endothelium.