Controlling the controls: GAD65 autoreactive T cells in type 1 diabetes.

The clinical onset of autoimmune (type 1) diabetes is associated with multiple immune abnormalities. First, the islets of Langerhans are infiltrated with macrophages and CD4 and CD8 T lymphocytes. This islet inflammation, or insulitis, is related to a major loss of islet β cells. In addition, the onset is strongly associated with autoantibodies against specific islet cell autoantigens. In particular, autoantibodies against the smaller isoform of glutamic acid decarboxylase (GAD65), the islet antigen-2 (IA-2, also known as ICA512), or insulin are common at the day of clinical onset. The simultaneous presence of all three autoantibodies is highly predictive of type 1 diabetes (1).