Article abstract
Nature Immunology 8, 1076 - 1085 (2007)
Published online: 26 August 2007 | doi:10.1038/ni1499
Lymph node chemokines promote sustained T lymphocyte motility without triggering stable integrin adhesiveness in the absence of shear forces
Eilon Woolf1, Irina Grigorova2, Adi Sagiv1, Valentin Grabovsky1, Sara W Feigelson1, Ziv Shulman1, Tanja Hartmann1, Michael Sixt3, Jason G Cyster2 & Ronen Alon1
Abstract
Lymphocyte motility in lymph nodes is regulated by chemokines, but the contribution of integrins to this motility remains obscure. Here we examined lymphocyte migration over CCR7-binding chemokines that 'decorate' lymph node stroma. In a shear-free environment, surface-bound lymph node chemokines but not their soluble counterparts promoted robust and sustained T lymphocyte motility. The chemokine CCL21 induced compartmentalized clustering of the integrins LFA-1 and VLA-4 in motile lymphocytes, but both integrins remained nonadhesive to ligands on lymphocytes, dendritic cells and stroma. The application of shear stress to lymphocytes interacting with CCL21 and integrin ligands promoted robust integrin-mediated adhesion. Thus, lymph node chemokines that promote motility and strongly activate lymphocyte integrins under shear forces fail to stimulate stable integrin adhesiveness in extravascular shear-free environments.
- Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
- Department of Microbiology and Immunology and Howard Hughes Medical Institute, University of California, San Francisco, California 94143, USA.
- Max Planck Institute of Biochemistry, Munich 82152, Germany.
Correspondence to: Ronen Alon1 e-mail: ronen.alon@weizmann.ac.il
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