To clarify this, Shulman et al. imaged the migration of effector T cells through inflamed endothelial barriers in vivo and in vitro. This approach revealed that, unlike naive or resting memory T cells, mouse effector T cells do not depend on chemokine receptor signalling for their adhesion on endothelial cells of inflamed blood vessels in the skin. Similarly, the adherence of human effector T cells on cytokine-stimulated human umbilical vein endothelial cells and their ability to crawl along these cells in the presence of shear flow in vitro was independent of chemokine receptor signalling. However, the constitutively high adhesion of effector T cells on endothelial cells required upregulation of the α4 integrin VLA4 and the β2 integrin LFA1 (but not their high-affinity conformations) on the T cell surface, as well as the activity of phospholipase Cγ1, which is crucial for integrin outside-in signalling. Moreover, integrin outside-in signalling, but not chemokine-induced signalling, was essential for T cell spreading and crawling.
So what is the role of chemokines and their receptors in effector T cell extravasation? Chemokine receptor signalling, together with LFA1 activation, was essential for transendothelial migration, with CC-chemokine receptor 2 (CCR2) being central in T helper 1 cell and effector CD8+ T cell extravasation. In addition to the CCR2 ligand CCL2, other chemokines were found to contribute to transendothelial effector T cell migration, and the required chemokine combination possibly varies depending on the type of inflammation and the location of the endothelial barrier.
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