TOLERANCE TO IDDM INDUCED BY CD4 ANTIBODIES IN NONOBESE DIABETIC MICEIS REVERSED BY CYCLOPHOSPHAMIDE

IDDM can be induced in nonobese diabetic (NOD) mice in several ways, i ncluding high doses of cyclophosphamide and transfer of diabetic splee n cells to sublethally irradiated recipients. It has previously been e stablished that transferred diabetes can be prevented by treatment wit h a nondepleting CD4 monoclonal antibody; however, we report herein th at cyclophosphamide-induced diabetes also can be prevented using this antibody. The protection induced by CD4 monoclonal antibody to transfe rred diabetes is maintained for a long period after cessation of antib ody treatment. However, cyclophosphamide can abrogate this induced tol erance and we report that this abrogation does not require new T-cells . During the course of the experimental work described, we observed th at the thymus had a suppressive effect on the expression of transferre d disease. Mice that were depleted of their peripheral T-cells showed a doubling of the time for disease expression if they were euthymic, c ompared with thymectomized mice.