Monday, October 15, 2007

Shear forces trigger T cell adhesion

At sites of inflammation, T lymphocytes bind to activated endothelium and move from the bloodstream into lymph nodes. Recruited T cells remain highly motile within the lymph node, scanning many dendritic cells and other antigen-presenting cells for cognate antigen. T cell motility is stimulated by chemokines, which can also promote adhesion by activating integrins.

Woolf and colleagues observed that many cells, including T cells themselves, express the same adhesion molecules and asked how premature arrest and clumping was avoided. To delineate the contributions of chemokines and adhesion molecules, they coated surfaces with CCL21, ICAM-1, or VCAM-1 and observed T cells moving on these surfaces. They found that surface-bound CCL21 stimulated T cell motility but soluble CCL21 did not. Although CCL21 also induced clustering of LFA-1 and VLA-4, these integrins did not mediate adhesion to their ligands ICAM-1 and VCAM-1. However, when T cells were exposed to shear stress, they rapidly developed strong adhesion to ICAM-1 or VCAM-1 (Figure). Video microscopy of T cells and lymph nodes cells obtained from mice deficient in adhesion molecules provided additional support for their conclusion that integrin-mediated adhesion, which is crucial to T cell recruitment from the bloodstream, is 'silenced' within the lymph node due to the absence of shear force.

Woolf et al. Nat Immunol. 2007 Oct;8(10):1076-85. Lymph node chemokines promote sustained T lymphocyte motility without triggering stable integrin adhesiveness in the absence of shear forces

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