Dendritic Cells in Islets of Langerhans Constitutively Present Beta Cell-Derived Peptides Bound to Their Class II MHC Molecules

Proc Natl Acad Sci U S A. 2008 Apr 22;105(16):6121-6. doi: 10.1073/pnas.0801973105. Epub 2008 Apr 21.

Abstract

Islets of Langerhans from normal mice contained dendritic cells (DCs) in the range of 8-10 per islet. DCs were found in several mouse strains, including those from lymphocyte-deficient mice. DCs were absent in islets from colony stimulating factor-1 deficient mice and this absence correlated with small size islets. Most DCs were found next to blood vessels and resided in islets for several days. Some DCs contained insulin-like granules, and most expressed peptide-MHC complexes derived from beta cell proteins. Islet DCs were highly effective in presenting beta cell antigens to CD4 T cells ex vivo. Presentation of beta cell-derived peptide-MHC complexes by DCs neither depended on islet inflammation nor correlated with the extent of spontaneous beta cell death. Periislet stroma DCs did not contain beta cell peptide-MHC complexes; however, 50% of DCs in pancreatic node were positive. Hence, presentation of high levels of beta cell antigens normally takes place by islet DCs, a finding that has to be placed in the perspective of autoimmune diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation*
  • Antigens, CD / analysis
  • Biological Assay
  • Cell Count
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Histocompatibility Antigens Class II / immunology*
  • Inflammation / immunology
  • Insulin / immunology*
  • Insulin-Secreting Cells / immunology*
  • Lymph Nodes / immunology
  • Mice
  • Mice, Inbred Strains
  • Peptides / analysis
  • Peptides / immunology

Substances

  • Antigens, CD
  • Histocompatibility Antigens Class II
  • Insulin
  • Peptides