T cells are required for the production of blister-inducing autoantibodies in experimental epidermolysis bullosa acquisita.

Abstract

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.

• Authors: Ana Gabriela Sitaru, Alina Sesarman, Sidonia Mihai, Mircea T Chiriac, Detlef Zillikens, Per Hultman, Werner Solbach, Cassian Sitaru
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 184 Issue 3 Pg. 1596-603 (Feb 01 2010) ISSN: 1550-6606 [Electronic] United States
• PMID: 20038644 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• Collagen Type VII
• Epitopes, T-Lymphocyte

Topics

• Amino Acid Sequence
• Animals
• Autoantibodies (adverse effects, biosynthesis)
• Blister (immunology, pathology)
• Cells, Cultured
• Collagen Type VII (administration & dosage, immunology)
• Disease Models, Animal
• Epidermolysis Bullosa Acquisita (immunology, pathology)
• Epitopes, T-Lymphocyte (immunology, metabolism)
• Lymphocyte Activation (immunology)
• Mice
• Mice, Inbred Strains
• Mice, Nude
• Molecular Sequence Data
• T-Lymphocyte Subsets (immunology, metabolism, pathology)