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Pancreatic NOD beta cells express MHC class II protein and the frequency of I-A(g7) mRNA-expressing beta cells strongly increases during progression to autoimmune diabetes |
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| Authors: | Walter U Toepfer T Dittmar K E J Kretschmer K Lauber J Weiss S Servos G Lechner O Scherbaum W A Bornstein S R Von Boehmer H Buer J |
| Affiliation: | (1) Department of Cellbiology and Immunology, German Research Centre for Biotechnology, Braunschweig, Germany;(2) Department of Molecular Biotechnology, German Research Centre for Biotechnology, Braunschweig, Germany;(3) German Diabetes Research Institute, University of Duesseldorf, Auf'm Hennekamp 65, 40225 Duesseldorf, Germany;(4) Department of Anatomy, University of Duesseldorf, Duesseldorf, Germany;(5) Department of Endocrinology, University of Duesseldorf, Duesseldorf, Germany;(6) INSERM U373, Institut Necker, Paris, France;(7) Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA;(8) Institute of Medical Microbiology, Hannover Medical School, Hannover, Germany |
| Abstract: | Aims/hypothesis In the NOD mouse model, attempts to show MHC class II expression by pancreatic beta cells were unsuccessful so far. We readdressed this question by analysing I-Ag7 expression in single pancreatic beta cells.Methods Single-cell multiplex RT PCR and single-cell immunofluorescence were used to study MHC class II expression in NOD and NOD/SCID beta cells.Results Pancreatic beta cells from NOD mice express the I-Ag7 protein as well as the corresponding mRNA. The frequency of MHC class II mRNA-expressing beta cells is drastically increased during the progression to overt diabetes. MHC class II protein is accumulated intracellularly, and invariant chain is co-expressed. Beta cells from 9- to 10-week-old NOD/SCID mice express MHC class II at the same low frequency as beta cells from 3-week-old NOD mice.Conclusion/interpretation NOD beta cells express I-Ag7 and could be a direct target of autoreactive CD4+ T cells. This MHC class II expression is triggered by infiltrating lymphocytes.Abbreviations APC antigen presenting cell - DC dendritic cell - IDDM insulin-dependent diabetes mellitus - Ii invariant chain - NOD non obese diabetic - PPI preproinsulin - SCID severe combined immunodeficiency |
| Keywords: | Beta cell MHC class II NOD mice Type-1-diabetes mellitus single-cell multiplex RT PCR |
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