Immunopathogenesis and immunotherapeutic approaches to type 1A diabetes.

It is now clear that type 1A (immune-mediated) diabetes develops in genetically susceptible individuals where, prior to the onset of overt hyperglycaemia, there is usually a long prodrome characterised by the presence of autoimmunity directed at islet beta cells. It is the destruction of these insulin-producing cells that results in loss of metabolic regulation and the resultant hyperglycaemia and severe sequelae of type 1A diabetes. An extensive body of animal data and a developing body of human studies are now addressing therapies directed at this root immune cause of type 1A diabetes. Therapies can be considered in terms of the disease stage at which they are applied and in terms of their effects on the immune system (e.g., generalised immunosuppression, immunomodulation, antigen-specific therapies and tolerance-inducing therapies). As T cells are the primary mediators of islet beta cell destruction, it is likely that improved therapies and monitoring of T cell autoimmunity will be necessary to develop a safe and effective therapy for type 1A diabetes.