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Fuchs, Y.F.* ; Adler, K.* ; Lindner, A.* ; Karasinsky, A.* ; Wilhelm, C.* ; Weigelt, M.* ; Balke, H. ; Förtsch, K. ; Mortler-Hildebrandt, L.F. ; Harlan, D.M.* ; Pechhold, K.* ; Ziegler, A.-G. ; Bonifacio, E.*

Igrp and insulin vaccination induce CD8+ T cell mediated autoimmune diabetes in the RIP-CD80GP mouse.

Clin. Exp. Immunol. 176, 199-206 (2014)
Postprint Manuscript DOI PMC
Open Access Green
Autoimmune diabetes is characterized by autoantigen-specific T cell-mediated destruction of pancreatic islet beta cells and CD8(+) T cells are key players during this process. We assessed whether the bitransgenic RIP-CD80 x RIP-LCMV-GP (RIP-CD80GP) mice may be a versatile antigen specific model of inducible CD8(+) T cell mediated autoimmune diabetes. Antigen-encoding DNA, peptide loaded dendritic cells, and antigen plus incomplete Freund's adjuvant were used for vaccination. Of 14 pancreatic proteins tested by DNA vaccination, murine pre-proinsulin 2 (100% of mice; median time after vaccination, 60 days), and Igrp (77%, 58 days) could induce diabetes. DNA vaccination with zinc transporter 8, Ia-2, Ia-2β, Gad67, Chromogranin A, IAPP, and Nkx2.2 induced diabetes development in 25-33% of mice, and with Gad65, Sgne1, Pdx1, Cel, glucagon, and control HBsAg in <20% of mice. Diabetes induction efficiency could be increased by DNA vaccination with a vector encoding a ubiquitin-antigen fusion construct. Diabetic mice had florid T cell islet infiltration. CD8(+) T cell targets of Igrp were identified with a peptide library based ELISpot assay, and diabetes could also be induced by vaccination with MHC class I restricted Igrp peptides loaded on mature dendritic cells. Vaccination with antigen plus incomplete Freund's adjuvant, which can prevent diabetes in other models, led to rapid diabetes development in the RIP-CD80GP mouse. We conclude that RIP-CD80GP mice are a versatile model of antigen specific autoimmune diabetes and may complement existing mouse models of autoimmune diabetes for evaluating CD8(+) T cell-targeted prevention strategies.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Autoimmunity ; Diabetes ; Antigens/peptides/epitopes ; Cytotoxic T Cells; Nod Mice; Adhesion Molecules; Interferon-gamma; Transgenic Mice; Recent-onset; Beta-cells; Pancreas; Mellitus; Expression; Responses
ISSN (print) / ISBN 0009-9104
e-ISSN 1365-2249
Journal Clinical & Experimental Immunology
Quellenangaben Volume: 176, Issue: 2, Pages: 199-206 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Hoboken
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research Type 1 (IDF)
Institute of Diabetes and Obesity (IDO)
Institute for Pancreatic Beta Cell Research (IPI)
German Center for Diabetes Reseach (DZD)