Mouse pancreatic beta cells express MHC class II and stimulate CD4+ T cells to proliferate

Yuxing Zhao, Nicholas A. Scott, Hong Sheng Quah, Balasubramanian Krishnamurthy, Francene Bond, Thomas Loudovaris, Stuart I. Mannering, Thomas W.H. Kay, Helen E. Thomas

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Type 1 diabetes results from destruction of pancreatic beta cells by autoreactive T cells. Both CD4+ and CD8+ T cells have been shown to mediate beta-cell killing. While CD8+ T cells can directly recognize MHC class I on beta cells, the interaction between CD4+ T cells and beta cells remains unclear. Genetic association studies have strongly implicated HLA-DQ alleles in human type 1 diabetes. Here we studied MHC class II expression on beta cells in nonobese diabetic mice that were induced to develop diabetes by diabetogenic CD4+ T cells with T-cell receptors that recognize beta-cell antigens. Acute infiltration of CD4+ T cells in islets occurred with rapid onset of diabetes. Beta cells from islets with immune infiltration expressed MHC class II mRNA and protein. Exposure of beta cells to IFN-γ increased MHC class II gene expression, and blocking IFN-γ signaling in beta cells inhibited MHC class II upregulation. IFN-γ also increased HLA-DR expression in human islets. MHC class II+ beta cells stimulated the proliferation of beta-cell-specific CD4+ T cells. Our study indicates that MHC class II molecules may play an important role in beta-cell interaction with CD4+ T cells in the development of type 1 diabetes.

Original languageEnglish (US)
Pages (from-to)2494-2503
Number of pages10
JournalEuropean Journal of Immunology
Issue number9
StatePublished - Sep 1 2015
Externally publishedYes


  • Autoimmune diabetes · CD4 T cells · MHC class II · Pancreatic beta cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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