Diabetes results from a late change in the autoimmune response of NOD mice

IDDM in the NOD mouse is the result of a chronic autoimmune process. NOD mice are shown to express benign autoimmunity that converts to a state of malignant autoimmunity and the development of IDDM. Young disease-prone NOD mice are in a state of benign autoimmunity that is correlated with a non-destructive response to islet tissue and the preservation of insulin-containing beta-cells. A proportion of mice with benign autoimmunity convert to having malignant autoimmunity. Clinical diabetes is diagnosed approximately 3 weeks from the development of malignant autoimmunity which is correlated with a destructive response to grafted islet tissue and extensive beta-cell destruction. We conclude that the development of clinical disease is correlated with a change in the state of autoimmunity, that is, from benign to malignant autoimmunity. (C) 1997 Academic Press Limited.