T Cells Are Required for the Production of Blister-Inducing Autoantibodies in Experimental Epidermolysis Bullosa Acquisita
| Autor: | Werner Solbach, Alina Sesarman, Mircea T. Chiriac, Cassian Sitaru, Detlef Zillikens, Ana Gabriela Sitaru, Per Hultman, Sidonia Mihai |
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| Rok vydání: | 2009 |
| Předmět: |
Epidermolysis bullosa acquisita
Collagen Type VII Immunogen Molecular Sequence Data Immunology Epitopes T-Lymphocyte Mice Nude Mice Inbred Strains Epidermolysis Bullosa Acquisita Lymphocyte Activation medicine.disease_cause Flow cytometry Autoimmunity Mice Blister T-Lymphocyte Subsets medicine Animals Immunology and Allergy Amino Acid Sequence Lymph node Cells Cultured Autoantibodies Autoimmune disease integumentary system medicine.diagnostic_test business.industry Autoantibody medicine.disease In vitro Disease Models Animal medicine.anatomical_structure business |
| Zdroj: | The Journal of Immunology. 184:1596-1603 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.0901412 |
| Popis: | Epidermolysis bullosa acquisita is a prototypical organ-specific autoimmune disease caused by autoantibodies against type VII collagen of the dermal-epidermal junction. Although mechanisms of autoantibody-induced blister formation were extensively characterized, the initiation of autoantibody production in autoimmune blistering diseases is still poorly defined. In the current study, we addressed the role of T cells for the production of blister-inducing autoantibodies in mice immunized with type VII collagen. To detect autoreactive type VII collagen-specific T cells, lymph node cells from immunized SJL mice were stimulated in vitro with recombinant Ag, and their proliferation was measured by radioactive thymidine incorporation and flow cytometry analysis of CFSE-labeled cells. Interestingly, using synthetic peptides of the immunogen, partly different T and B cell epitopes in mice immunized with type VII collagen were demonstrated. In contrast to wild-type mice, immunization with type VII collagen of SJL athymic nude mice lacking T cells did not induce an autoimmune response and blistering phenotype. Importantly, SJL nude mice repleted with T cells from immunized wild-type mice showed a robust and durable autoantibody production resulting in subepidermal blistering disease in the recipients. Our present results demonstrate that T cells are required for the initiation of autoimmunity against type VII collagen in experimental epidermolysis bullosa acquisita and provide a basis for developing T cell-directed immunomodulatory strategies for this and related autoimmune diseases. |
| Databáze: | OpenAIRE |
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