Peripheral antigen-expressing cells in type 1 diabetes.

Studies in both humans and rodent models provide new insight into key mechanisms regulating tolerance to self-molecules. There is evidence that tissue-specific molecules are expressed in the thymus and peripheral lymphoid tissues (PLTs) by specialized antigen-presenting cells (APCs), and that such expression is critical for self-tolerance. Insulin, a key hormone exclusively produced by pancreatic beta cells and a critical autoantigen in type 1 diabetes, provides an excellent example of a molecule with tissue-restricted expression that is ectopically expressed by APCs in both thymus and PLTs. APCs may play a role in insulin presentation in both the central and peripheral immune system. Functional data from several transgenic and knockout mouse models, some specific for the expression of insulin, help dissect the significance of self-molecule presentation by APCs and its role in autoimmune diabetes.