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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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-A(g7) 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-A(g7) 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-A(g7) and could be a direct target of autoreactive CD4+ T cells. This MHC class II expression is triggered by infiltrating lymphocytes.
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