Differential Roles for Endothelial ICAM-1, ICAM-2, and VCAM-1 in Shear-Resistant T Cell Arrest, Polarization, and Directed Crawling on Blood-Brain Barrier Endothelium

作者：Steiner Oliver; Coisne Caroline; Cecchelli Romeo; Boscacci Remy; Deutsch Urban; Engelhardt Britta^*; Lyck Ruth

来源：The Journal of Immunology, 2010, 185(8): 4846-4855.

DOI：10.4049/jimmunol.0903732

Endothelial ICAM-1 and ICAM-2 were shown to be essential for T cell diapedesis across the blood-brain barrier (BBB) in vitro under static conditions. Crawling of T cells prior to diapedesis was only recently revealed to occur preferentially against the direction of blood flow on the endothelial surface of inflamed brain microvessels in vivo. Using live cell-imaging techniques, we prove that Th1 memory/effector T cells predominantly crawl against the direction of flow on the surface of BBB endothelium in vitro. Analysis of T cell interaction with wild-type, ICAM-1-deficient, ICAM-2-deficient, or ICAM-1 and ICAM-2 double-deficient primary mouse brain microvascular endothelial cells under physiological flow conditions allowed us to dissect the individual contributions of endothelial ICAM-1, ICAM-2, and VCAM-1 to shear-resistant T cell arrest, polarization, and crawling. Although T cell arrest was mediated by endothelial ICAM-1 and VCAM-1, T cell polarization and crawling were mediated by endothelial ICAM-1 and ICAM-2 but not by endothelial VCAM-1. Therefore, our data delineate a sequential involvement of endothelial ICAM-1 and VCAM-1 in mediating shear-resistant T cell arrest, followed by endothelial ICAM-1 and ICAM-2 in mediating T cell crawling to sites permissive for diapedesis across BBB endothelium. The Journal of Immunology, 2010, 185: 4846-4855.

• 出版日期2010-10-15