T cells are required for the production of blister-inducing autoantibodies in experimental epidermolysis bullosa acquisita.
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.
Sitaru
Ana Gabriela
AG
Institute for Medical Microbiology and Hygiene, University of Lübeck, Lübeck, Germany.
Sesarman
Alina
A
Mihai
Sidonia
S
Chiriac
Mircea T
MT
Zillikens
Detlef
D
Hultman
Per
P
Solbach
Werner
W
Sitaru
Cassian
C
D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000009:adverse effects / Q000096:biosynthesis*; D001768:Blister / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D024143:Collagen Type VII / Q000008:administration & dosage / Q000276:immunology*; D004195:Disease Models, Animal; D016107:Epidermolysis Bullosa Acquisita / Q000276:immunology* / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D008969:Molecular Sequence Data; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D001323:Autoantibodies; D024143:Collagen Type VII; D018984:Epitopes, T-Lymphocyte