Recurrence of insulitis in the NOD mouse after early prolonged anti-CD4 monoclonal antibody treatment.
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-CD4 mAb 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 pancreas 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 less than 0.01). At 180 days of age the insulitis grade in treated mice was 29 +/- 23% compared with 47 +/- 22% in aged 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-CD4 mAb treatment does not therefore appear to produce a tolerant state so averting insulitis development and, insulitis can still develop in older NOD mice.
Charlton
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Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Mandel
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D001327:Autoimmune Diseases / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D015704:CD4 Antigens / Q000037:antagonists & inhibitors*; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology; D005260:Female; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology; D008212:Lymphocyte Depletion; D051379:Mice; D008817:Mice, Mutant Strains; D012008:Recurrence; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D015704:CD4 Antigens