title: Expression of Wiskott-Aldrich syndrome protein in dendritic cells regulates synapse formation and activation of naive CD8+ T cells.
abstract: The Wiskott-Aldrich syndrome protein (WASp) is a key regulator of actin polimerization in hematopoietic cells. Mutations in WASp cause a severe immunodeficiency characterized by defective initiation of primary immune response and autoimmunity. The contribution of altered dendritic cells (DCs) functions to the disease pathogenesis has not been fully elucidated. In this study, we show that conventional DCs develop normally in WASp-deficient mice. However, Ag targeting to lymphoid organ-resident DCs via anti-DEC205 results in impaired naive CD8(+) T cell activation, especially at low Ag doses. Altered trafficking of Ag-bearing DCs to lymph nodes (LNs) accounts only partially for defective priming because correction of DCs migration does not rescue T cell activation. In vitro and in vivo imaging of DC-T cell interactions in LNs showed that cytoskeletal alterations in WASp null DCs causes a reduction in the ability to form and stabilize conjugates with naive CD8(+) T lymphocytes both in vitro and in vivo. These data indicate that WASp expression in DCs regulates both the ability to traffic to secondary lymphoid organs and to activate naive T cells in LNs.
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
authors.forename: Julian
authors.initials: J
authors.lastname: Pulecio
authors.forename: Elisa
authors.initials: E
authors.lastname: Tagliani
authors.forename: Alix
authors.initials: A
authors.lastname: Scholer
authors.forename: Francesca
authors.initials: F
authors.lastname: Prete
authors.forename: Luc
authors.initials: L
authors.lastname: Fetler
authors.forename: Oscar R
authors.initials: OR
authors.lastname: Burrone
authors.forename: Federica
authors.initials: F
authors.lastname: Benvenuti
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D051316:Wiskott-Aldrich Syndrome Protein / Q000276:immunology / Q000378:metabolism*
chemical_list: D051316:Wiskott-Aldrich Syndrome Protein