PMID:22804504

Citation	Lafouresse, F, Cotta-de-Almeida, V, Malet-Engra, G, Galy, A, Valitutti, S and Dupré, L (2012) Wiskott-Aldrich syndrome protein controls antigen-presenting cell-driven CD4+ T-cell motility by regulating adhesion to intercellular adhesion molecule-1. Immunology 137:183-96
Abstract	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.
Links	PubMed PMC3461399 Online version:10.1111/j.1365-2567.2012.03620.x
Keywords	Antigen-Presenting Cells/immunology; CD4-Positive T-Lymphocytes/cytology; CD4-Positive T-Lymphocytes/immunology; Cell Adhesion; Cell Movement; Cells, Cultured; Humans; Intercellular Adhesion Molecule-1/immunology; RNA, Small Interfering/genetics; Wiskott-Aldrich Syndrome Protein/genetics; Wiskott-Aldrich Syndrome Protein/immunology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:WASP	involved_in	GO:2000146: negative regulation of cell motility	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:WASP	involved_in	GO:0002625: regulation of T cell antigen processing and presentation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:WASP		GO:0002625: regulation of T cell antigen processing and presentation	ECO:0000315:		P		Fig 7b shows that the stained WASP-deficient T-cells show a reduction in the presence of antigens just on the mid body. Instead they are spread all the way down to the uropod.	complete CACAO 5733
HUMAN:WASP		GO:2000146: negative regulation of cell motility	ECO:0000315:		P		Fig 2a shows that in the presence of JY cells, the motility of WASP deficient T-cells is significantly increased.	complete CACAO 5734

References

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