Aberrant expression of HLA-DR antigens by insulin-containing beta-cells in recent-onset type I diabetes mellitus

The biosociology of pancreatic B cells

“…Our observations have demonstrated that these cells may exhibit the capability to incorporate fragments of damaged B cells [52]. Additional cell markers may thus become necessary to distinguish, in pancreatic sections, insulin-containing myeloid cells from pancreatic B cells with induced MHC-class II expression, in particular since both cell types can be associated to processes of B-cell destruction [56,57].…”

Pancreatic NOD beta cells express MHC class II protein and the frequency of I-Ag7 mRNA-expressing beta cells strongly increases during progression to autoimmune diabetes

“…MHC class II expression on beta cells has been shown to be inducible in vitro by IFN-γ and TNF-α in normal mouse islet beta cells [6,11], on cultured human islets [7] and by IFN-γ alone on beta cells from diabetesprone BB rats [12]. Moreover, beta cells from the pancreas of patients with recent-onset Type-1-diabetes [9,13] as well as from diabetes-prone BB rats [10] express MHC class II molecules. It has also been shown that I-A g7 itself is an autoantigen in IDDM in the NOD mouse [16].…”

“…A series of publications also provided evidence that beta cells can be induced to express MHC class II molecules [6,7,8,9,10,11,12,13]. However, since it has been reported that MHC class II molecules in NOD islets are expressed exclusively by CD45+ cells [14], that is, cells of haematopoietic origin, it is generally accepted that NOD beta cells are I-A g7 -negative and therefore cannot directly be recognised by self-reactive CD4+ T cells [15].…”

Fasting and meal-stimulated residual beta cell function is positively associated with serum concentrations of proinflammatory cytokines and negatively associated with anti-inflammatory and regulatory cytokines in patients with longer term type 1 diabetes

“…It is conceivable that the presence of beta cells promotes beta cell-directed immune reactivity and inflammation. Indeed, histological post mortem analyses of pancreases from patients with type 1 diabetes have demonstrated local inflammation of the islets only if beta cells were still present [24]. The insulitis process is thought to decrease during the years after onset of diabetes, in parallel with the loss of residual beta cell function.…”