The β-Cell in Type 1 Diabetes Pathogenesis: A Victim of Circumstances or an Instigator of Tragic Events?

Recent reports have revived interest in the active role that β-cells may play in type 1 diabetes pathogenesis at different stages of disease. In some studies, investigators suggested an initiating role and proposed that type 1 diabetes may be primarily a disease of β-cells and only secondarily a disease of autoimmunity. This scenario is possible and invites the search for environmental triggers damaging β-cells. Another major contribution of β-cells may be to amplify autoimmune vulnerability and to eventually drive it into an intrinsic, self-detrimental state that turns the T cell-mediated homicide into a β-cell suicide. On the other hand, protective mechanisms are also mounted by β-cells and may provide novel therapeutic targets to combine immunomodulatory and β-cell protective agents. This integrated view of autoimmunity as a disease of T-cell/β-cell cross talk will ultimately advance our understanding of type 1 diabetes pathogenesis and improve our chances of preventing or reversing disease progression.