Skin pathology in Wiskott-Aldrich syndrome mice is caused by hyperactive CD8+ T cells and increased cross-presentation by DCs (P1048)
| Autor: | Marisa Baptista, Carin Dahlberg, Agne Liedén, I-Chun Kuo, Karen Sunahara, Robert Wallin, Mattias Forsell, Scott Snapper, Liv Eidsmo, Annika Scheynius, Mikael Karlsson, Nylén Susanne, Lisa Westerberg |
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| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 190:65.25-65.25 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.190.supp.65.25 |
| Popis: | It remains puzzling how immunodeficiency with hypo-responsive cells can be associated with increased immune cell activation to seemingly harmless substances such as allergens. Here, we have investigated skin pathology in the severe primary immunodeficiency Wiskott-Aldrich syndrome (WAS). Wildtype and WAS protein-deficient (WASp KO) mice were challenged with the allergen Der p 2 to induce eczema or infected with Leishmania major to induce robust skin inflammation. Der p 2 challenge of wildtype mice induced eczema with epidermal hyperplasia and egress of Langerhans cells from the skin. WASp KO mice had increased accumulation of mature DCs in the skin and, in contrast to wildtype cells, Der p 2 induced expansion of WASp KO CD8+ T cells that produced IFNγ. Similar to challenge with Der p 2 and unlike wildtype mice, WASp KO mice infected with L. major showed a skewed immune response with increased expansion of IFNγ-producing CD8+ T cells in the draining lymph node. Finally, we show that WASp KO DCs have increased capacity to cross-present exogenous antigen and activate CD8+ T cells. Our results imply that WASp deficiency in skin inflammation causes a breach in tolerance and skews the immune system to DC mediated CD8+ T cell responses at incorrect sites. |
| Databáze: | OpenAIRE |
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