Tolerance to IDDM Induced by CD4 Antibodies in Nonobese Diabetic Mice is Reversed by Cyclophosphamide

IDDM can be induced in nonobese diabetic (NOD) mice in several ways, including high doses of cyclophosphamide and transfer of diabetic spleen cells to sublethally irradiated recipients. It has previously been established that transferred diabetes can be prevented by treatment with a nondepleting CD4 monoclonal antibody; however, we report herein that cyclophosphamide-induced diabetes also can be prevented using this antibody. The protection induced by CD4 monoclonal antibody to transferred diabetes is maintained for a long period after cessation of antibody treatment. However, cyclophosphamide can abrogate this induced tolerance and we report that this abrogation does not require new T-cells. During the course of the experimental work described, we observed that the thymus had a suppressive effect on the expression of transferred disease. Mice that were depleted of their peripheral T-cells showed a doubling of the time for disease expression if they were euthymic, compared with thymectomized mice.