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

Ana Gabriela Sitaru, Alina Sesarman, Sidonia Mihai, Mircea T. Chiriac, Detlef Zillikens, Per Hultman, Werner Solbach, Cassian Sitaru*

*Korrespondierende/r Autor/-in für diese Arbeit
33 Zitate (Scopus)

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.
OriginalspracheEnglisch
ZeitschriftJournal of Immunology
Jahrgang184
Ausgabenummer3
Seiten (von - bis)1596-1603
Seitenumfang8
ISSN0022-1767
DOIs
PublikationsstatusVeröffentlicht - 01.02.2010

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