Wiskott–Aldrich syndrome protein controls antigen-presenting cell-driven CD4+ T-cell motility by regulating adhesion to intercellular adhesion molecule-1
2012
T-cell scanning for antigen-presenting cells (APC) is a finely tuned process.
Whereas non-cognate APC trigger T-cell motility via chemokines
and intercellular adhesion molecule-1 (ICAM-1), cognate APC deliver a
stop signal resulting from antigen recognition. We tested in vitro the contribution
of the actin cytoskeleton regulator Wiskott–Aldrich syndrome
protein (WASP) to the scanning activity of primary human CD4+ T cells.
WASP knock-down resulted in increased T-cell motility upon encounter
with non-cognate dendritic cells or B cells and reduced capacity to stop
following antigen recognition. The high motility of WASP-deficient T cells
was accompanied by a diminished ability to round up and to stabilize
pauses. WASP-deficient T cells migrated in a normal proportion towards
CXCL12, CCL19 and CCL21, but displayed an increased adhesion and
elongation on ICAM-1. The elongated morphology of WASP-deficient
T cells was related to a reduced confinement of high-affinity lymphocyte
function-associated antigen 1 to the mid-cell zone. Our data therefore
indicate that WASP controls CD4+ T-cell motility upon APC
encounter by regulating lymphocyte function-associated antigen 1 spatial
distribution.
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