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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)
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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
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
Language english
Publication Year 2014
HGF-reported in Year 2014
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
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research (IDF)
Institute of Diabetes and Obesity (IDO)
Institute of Pancreatic Islet Research (IPI)
German Center for Diabetes Reseach (DZD)
POF-Topic(s) 30201 - Metabolic Health
90000 - German Center for Diabetes Research
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-502100-001
G-501900-229
PubMed ID 24387268
DOI 10.1111/cei.12263
WOS ID WOS:000334030600007
Erfassungsdatum 2014-01-31
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