Effect of antiserum to monoclonal anti-islet cell surface antibody on pancreatic insulitis in non-obese diabetic mice.
Immunotherapeutic intervention has been studied in non-obese diabetic (NOD) mice. Twenty-five male NOD mice aged 6 weeks were treated with anti-mouse T lymphocyte serum (ATS), N-(2-carboxyphenyl)-4-chloroanthranilic acid disodium salt (CCA); a non-specific immunostimulant which seems to potentiate the suppressor T cell activity, and antiserum raised against previously reported monoclonal antibody 3A4 to the surface of islet cells. Pancreatic islets from NOD mice sacrificed at 12 weeks of age were scored morphologically for the severity and the frequency of insulitis. Both the severity of insulitis in each islet and the frequency of insulitis-positive islets in each pancreas were reduced in the groups treated with ATS (group B), antiserum to 3A4 (group D) and a combination of antiserum plus CCA (group E) in comparison with other groups (control: group A and CCA: group C). At 8 weeks of age, the binding capacities of sera to insulinoma cells measured by protein A radioligand assay were significantly decreased in the groups treated with antiserum to 3A4 (groups D and E) as compared with those in the other groups. These results suggest that both ATS and antiserum to 3A4 prevent the occurrence and the progress of insulitis in NOD mice, but the immunosuppressive mechanisms differ from each other; therefore, combination therapy with these suppressants may be more effective in the prevention of Type 1 diabetes mellitus.