Autoimmune Diabetes: the Involvement of Benign and Malignant Autoimmunity

Our studies in the NOD mouse demonstrate that the autoimmune response can be either benign or malignant. In the former case </=10% of the islets in the pancreas are damaged. The latter is associated with massive islet damage which leads to the development of clinical disease within 2-3 weeks. From the time of weaning up to 70-80 days of age all male and female NOD mice are in a benign state of autoimmunity. After that time animals move, in an unpredictable way, into the malignant state of autoimmunity. As a result, animals >/=100 days of age make up a heterogeneous group where some are in a benign state of autoimmunity, which can continue for a further |LX200 days, others are in a state of transition to the malignant state of autoimmunity, and others have a fully malignant autoimmune response and are diabetic. This heterogeneity developing within members of the population, in terms of pancreatic damage, is not consistent with the proposal that autoimmune islet damage in the NOD mouse is a slow, progressive process affecting all disease prone members of the population. In the NOD mouse, massive islet destruction is a late event in the autoimmune process and only develops following the conversion of the autoimmune response from the benign to the malignant state.