CHECKPOINTS IN THE PROGRESSION OF AUTOIMMUNE-DISEASE - LESSONS FROM DIABETES MODELS

In the last few years, data from experiments employing transgenic mode ls of autoimmune diseases have strengthened a particular concept of au toimmunity: disease results not so much from cracks in tolerance induc tion systems, leading to the generation of an anti-self repertoire, as from the breakdown of secondary systems that keep these cells in chec k. T cells with anti-self specificities are readily found in disease-f ree individuals but ignore target tissues. This is also the case in so me transgenic models, in spite of overwhelming numbers of autoreactive cells, In other instances, local infiltration and inflammation result , but they are well tolerated for long periods of time and do not term inally destroy target tissue. We review the possible molecular and cel lular mechanisms that underlie these situations, with a particular emp hasis on the destruction of pancreatic beta cells in transgenic models of insulin-dependent diabetes.