Intercellular Adhesion Molecule 1 Mediates Migration of Th1 and Th17 Cells Across Human Retinal Vascular Endothelium
Intercellular Adhesion Molecule 1 Mediates Migration of Th1 and Th17 Cells Across Human Retinal Vascular Endothelium
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DOI：
10.1167/iovs.13-12058
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发表时间：
2013-10-01
影响因子：
4.4
通讯作者：
Smith, Justine R.
中科院分区：
文献类型：
--
作者：
Bharadwaj, Arpita S.;Schewitz-Bowers, Lauren P.;Smith, Justine R.
目的.视网膜的自身免疫性炎症导致大多数受影响个体的视力丧失。Th 1或Th 17细胞从循环穿过视网膜血管内皮进入眼睛时引发疾病。我们研究了人Th 1和Th 17极化细胞穿过模拟人视网膜内皮的能力，并检测了IgG超家族成员在这一过程中的作用。使用两种Th 1和Th 17极化方案从人外周血CD 4（+）T细胞产生Th 1和Th 17极化细胞群。在用人视网膜内皮细胞接种transwell膜后，在Boyden室中进行18小时以上的跨内皮迁移测定。在一些测定中，将细胞间粘附分子1（ICAM-1）、血管细胞粘附分子1（VCAM-1）或活化的白细胞粘附分子（ALCAM）阻断抗体或同种型和浓度匹配的对照抗体加入到上室中。Th 1-和Th 17-极化细胞同样有效地迁移通过人视网膜内皮单层。IL-17（+）IFN-γ（-）Th 17极化细胞的百分比在迁移后降低。阻断ICAM-1，而不是VCAM-1或ALCAM，显著降低了大多数人供体Th 1和Th 17极化细胞的迁移。在其他文献的背景下，跨内皮迁移，我们的研究结果说明了调查特定的组织和血管内皮细胞时，考虑辅助性T细胞迁移在自身免疫性炎症的重要性。我们的研究结果进一步表明，虽然葡萄膜炎和其他自身免疫性疾病中特异性粘附分子的参与可能是可能的，但这些可能并不普遍适用于个体患者。这些观察结果与粘连阻滞剂用于治疗目的有关。
PURPOSE. Autoimmune inflammation of the retina causes vision loss in the majority of affected individuals. Th1 or Th17 cells initiate the disease on trafficking from the circulation into the eye across the retinal vascular endothelium. We investigated the ability of human Th1- and Th17-polarized cells to cross a simulated human retinal endothelium, and examined the role of IgG superfamily members in this process.METHODS. Th1-and Th17-polarized cell populations were generated from human peripheral blood CD4(+) T cells, using two Th1-and Th17-polarizing protocols. Transendothelial migration assays were performed over 18 hours in Boyden chambers, after seeding the transwell membrane with human retinal endothelial cells. In some assays intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), or activated leukocyte cell adhesion molecule (ALCAM) blocking antibody, or isotype-and concentration-matched control antibody, was added to the upper chambers.RESULTS. Th1-and Th17-polarized cells migrated equally efficiently across the human retinal endothelial monolayer. The percentage of IL-17(+) IFN-gamma(-) Th17-polarized cells was reduced following migration. Blocking ICAM-1, but not VCAM-1 or ALCAM, significantly reduced migration of Th1-and Th17-polarized cells for a majority of human donors.CONCLUSIONS. Taken in the context of other literature on transendothelial migration, our results illustrate the importance of investigating the specific tissue and vascular endothelium when considering helper T cell migration in autoimmune inflammation. Our findings further indicate that while generalizations about involvement of specific adhesion molecules in uveitis and other autoimmune disease may be possible, these may not apply to individual patients universally. The observations are relevant to the use of adhesion blockade for therapeutic purposes.