title: Defective actin reorganization and polymerization of Wiskott-Aldrich T cells in response to CD3-mediated stimulation.
abstract: The Wiskott-Aldrich syndrome (WAS) is a severe immunodeficiency and platelet deficiency disease arising from mutation(s) in the WASP gene, which in normal cells encodes an intracellular protein able to interact with other proteins relevant to the control of cytoskeleton organization. Immunodeficiency is mainly due to T-cell progressive malfunction. Salient defects of WAS T cells are a CD3-restricted impairment in proliferative responses and cytoskeletal abnormalities, including the frequent appearance of T cells with atypical morphology. We have investigated the possibility that the CD3-restricted defect and some of the cytoskeletal defects of WAS T cells are linked. For this purpose, we immortalized by means of infection with Herpesvirus Saimiri a number of previously described allospecific WAS T-cell lines. The resulting cells preserve the surface, molecular, and functional phenotypes of their parental lines, including a negligible WASP mRNA expression as well as the CD3-restricted defect and cytoskeleton abnormalities. Results show that, in CD3-stimulated WAS T cells, the pattern of temporal changes in cell shape and F-actin distribution is substantially different from that of control cells. Furthermore, polymerization of actin, a critical step in the CD3-mediated cytoskeleton reorganization, does not occur in WAS T-cell lines in response to OKT3 stimulation. In conclusion, our data link both CD3 and cytoskeletal defects in WAS T cells, strongly suggesting that cytoskeleton abnormalities are an underlying cause for WAS immunodeficiency.
authors.affiliation: Immunology Unit, University of Granada School of Medicine, Spain.
authors.forename: M D
authors.initials: MD
authors.lastname: Gallego
authors.forename: M
authors.initials: M
authors.lastname: Santamaría
authors.forename: J
authors.initials: J
authors.lastname: Peña
authors.forename: I J
authors.initials: IJ
authors.lastname: Molina
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism*; D002455:Cell Division; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000648:ultrastructure; D005786:Gene Expression Regulation; D006567:Herpesvirus 2, Saimiriine; D006801:Humans; D008213:Lymphocyte Activation; D008855:Microscopy, Electron, Scanning; D010641:Phenotype; D011108:Polymers; D011487:Protein Conformation; D013499:Surface Properties; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D014923:Wiskott-Aldrich Syndrome / Q000097:blood / Q000276:immunology*
chemical_list: D000199:Actins; D017252:CD3 Complex; D011108:Polymers