Wiskott-Aldrich syndrome protein controls antigen-presenting cell-driven CD4+ T-cell motility by regulating adhesion to intercellular adhesion molecule-1.
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.
INSERM, U1043, Toulouse, France.
Fanny
F
Lafouresse
Vinicius
V
Cotta-de-Almeida
Gema
G
Malet-Engra
Anne
A
Galy
Salvatore
S
Valitutti
Loïc
L
Dupré
D000938:Antigen-Presenting Cells / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D034741:RNA, Small Interfering / Q000235:genetics; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics / Q000276:immunology*
D034741:RNA, Small Interfering; D051316:Wiskott-Aldrich Syndrome Protein; D018799:Intercellular Adhesion Molecule-1