Recurrence of Insulitis in the Nod Mouse After Early Prolonged Anti-CD4 Monoclonal Antibody Treatment

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Abstract
The treatment of young NOD mice with continuous anti-CD4 mAb administration has previously been shown to prevent insulitis from developing. It has also been shown that insulitis, once present, can be abolished by anti-CD4 mAb treatment, but that the insulitis recurs after treatment stops. We have studied the effect of treating young NOD/Wehi mice with a limited course of anti-CD4mAb to determine if any long term prevention of insulitis ensued. Anti-CD4 mAb (H129.19) was given i.p. weekly to 10 female NOD/Wehi mice from 25–100 days of age. Control mice received no treatment. The pancreases of the mice were examined histologically at 100 and 180 days of age and severity of insulitis graded from 0–100% The insulitis grade in treated mice at 100 days was 5 ± 2% compared with 29 + 26% in age matched control mice (p < 0.01). At 180 days of age the insulitis grade in treated mice was 29 ± 23% compared with 47 ± 22% in age matched controls (NS). Thus insulitis was prevented from developing by early treatment with anti-CD4 mAb but developed later when treatment was stopped. Early anti-CD4mAb treatment does not therefore appear to produce a tolerant state so averting insulitis development and, insulitis can still develop in older NOD mice.