Immune abnormalities in the diabetic New Zealand obese (NZO) mouse: Insulin treatment partially suppresses splenic hyperactivity measured by flow cytometric analysis

Immune abnormalities in both the humoral and cell-mediated immune systems were found in New Zeland obese (NZO) mice, a model of diabetes associated with autoimmune disease. Both the formation of anti-sheep red blood cell plaques and mitogen stimulation of NZO spleen cells were significantly decreased compared to normal strains of mice. In addition to perturbations of splenic lymphocyte function, the enlarged spleens of NZO mice demonstrated increased cycling cells as measured by flow cytometric analysis of the DNA content of individual cells. These abnormalities are similar but less pronounced than those found in another autoimmune model, the New Zealand black (NZB) strain. The pancreases of diabetic NZO mice contained a higher fraction of nuclei with greater than 2c amount of DNA. Chronic insulin administration decreased the percentages of splenic proliferating cells and polyploid pancreas cells in NZO mice. In addition, insulin treatment of NZO mice decreased spleen weights and serum glucose levels. Chronic insulin treatment did not alter these parameters in either nondiabetic Balb/c or autoimmune NZB mice. Thus, the features of the NZO strain which serve as both an autoimmunity model and a diabetes model can be dissociated. Insulin treatment had a unique effect on NZO traits but not on NZB traits even though many of these traits were present in both strains. In conclusion, although autoimmunity may underlie the diseases of both the NZO and the NZB strains, the amelioration of some of the features of the NZO strain by insulin may represent the beneficial effects of insulin on the metabolic control of cellular function in NZO mice. © 1985.