The central role of antigen presentation in islets of Langerhans in autoimmune diabetes

Abstract

The islets of Langerhans normally contain resident antigen presenting cells (APCs), which in normal conditions are mostly represented by macrophages, with a few dendritic cells (DC). We present here the features of these islet APCs, making the point that they have a supportive function in islet homeostasis. Islet APCs express high levels of major histocompatibility complexes (MHC) molecules on their surfaces and are highly active in antigen presentation in the autoimmune diabetes of the NOD mouse: they do this by presenting peptides derived from molecules of the β-cells. These APCs also are instrumental in the localization of diabetogenic T cells into islets. The islet APC present exogenous peptides derived from secretory granules of the β-cell, giving rise to unique peptide-MHC complexes (pMHC) that activate those non-conventional T cells that bypass thymus selection.

Figure 1. Examination of islets for myeloid cells, T cells and myeloid transcriptional analysis

A) Islet of 8 week-old NOD.Rag1^-/- mouse showing myeloid cells (CD11c+) and blood vessels (PECAM-1+). Note the close apposition of CD11c+ cells with vessels. Inset shows the apposition between islet myeloid cell and vessel. B) Islet from 6 week-old NOD female mice stained for blood vessels (PECAM-1+), islet myeloid cells (CD11c+), and T cells (CD4+). Insets show contacts between islet myeloid cells and CD4 T cells. White bars represent 50 μm. Panel B) and C) taken from Ref. with permission. C) Microarray identification of myeloid gene signatures in islets of Langerhans. The heat map shows a hierarchically clustered gene subset that is enriched for macrophage/myeloid genes in NOD mice (2, 4 and 6 weeks), C57BL/6 and NOD.Rag-1^-/- (6 weeks). Color intensity is based on the row normalized log₂ scaled relative expression. The subset of genes represented in Panel C) is derived from the analysis detailed in Ref. .