Wiskott–Aldrich syndrome protein controls antigen‐presenting cell‐driven CD4+ T‐cell motility by regulating adhesion to intercellular adhesion molecule‐1

Summary 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.