Insulin teaches a new lesson in tolerance

The immune system must be educated to discriminate between the body's own tissues ('self') and foreign pathogenic microorganisms (non-self). This ability is acquired by T lymphocytes in the thymus (central tolerance) and it is further refined by peripheral tolerance. Errors in discrimination potentially result in autoimmune diseases, such as type 1 diabetes, in which the insulin-producing beta cells of the pancreas are destroyed by T lymphocytes. In this issue of The EMBO Journal, Fan et al (2009) describe how a failure of central tolerance to insulin causes diabetes in a mouse strain resistant to spontaneous autoimmune diabetes. Conversely, enhanced central tolerance to insulin can prevent diabetes in diabetes-prone mice (French et al, 1997). Inducing or preventing diabetes by controlling the immune response to insulin is consistent with autoimmunity being the cause of diabetes rather than a secondary response to tissue damage.