REGULATION OF AUTOIMMUNE DIABETES - CHARACTERISTICS OF NON-ISLET-ANTIGEN SPECIFIC THERAPIES

Non-islet-antigen specific treatments have been shown to alter the nat ural history of insulin dependent diabetes in both the non-obese diabe tic (NOD) mouse and in recently diagnosed patients. However, concerns have been raised regarding the possibility that non-islet-antigen spec ific therapy may trade cell mediated autoimmunity for antibody depende nt autoimmunity. Female NOD mice at approximately 70 days of age were treated with the non-islet-antigen specific agents complete Freund's a djuvant (CFA) and Bacillus Calmette-Guerin (BCG) and assayed for the d evelopment of antibody mediated autoimmunity at 300 days of age. Autoa ntibodies to red cells were not detected in any of the BCG (n = 19) or CFA (n = 15) treated animals, while 2 of 13 age-matched NOD animals h ad autoantibodies to red cells, shown by a positive direct Coomb's tes t. Anti-nuclear autoantibodies and complement deposition in the renal glomeruli were not significantly increased in the treated animals as c ompared to age-matched non-diabetic mice. The relative effectiveness o f CFA and BCG treatment was examined in terms of the ability of these agents to preserve insulin containing islets. Complete Freund's adjuva nt treatment was found to be more effective in preserving insulin cont aining islets when compared to BCG treatment. This study demonstrates that it is possible to inhibit the development of autoimmune diabetes without increasing the probability that treated animals will develop a ntibody dependent autoimmunity.