Expression of Wiskott-Aldrich Syndrome Protein in Dendritic Cells Regulates Synapse Formation and Activation of Naive CD8+ T Cells
| Autor: | Oscar R. Burrone, Elisa Tagliani, Federica Benvenuti, Francesca Prete, Alix Scholer, Julian Pulecio, Luc Fetler |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
T cell
Immunology Priming (immunology) macromolecular substances CD8-Positive T-Lymphocytes Biology Lymphocyte Activation medicine.disease_cause Autoimmunity Mice medicine Animals Immunology and Allergy Cytotoxic T cell Follicular dendritic cells Wiskott–Aldrich syndrome protein hemic and immune systems Dendritic Cells Mice Mutant Strains Cell biology Haematopoiesis medicine.anatomical_structure biology.protein Lymph Nodes Wiskott-Aldrich Syndrome Protein CD8 |
| Zdroj: | The Journal of Immunology. 181:1135-1142 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.181.2.1135 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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