Preventive Effect of Monoclonal Anti-L3T4 Antibody on Development of Diabetes in NOD Mice

We analyzed the surface phenotypes of infiltrated cells in pancreases of nonobese diabetic (NOD) mice with monoclonal antibodies to mouse lymphocytes. Most of the infiltrated cells were Thy1⁺ and Ly1⁺ T-lymphocytes, and most of them were L3T4⁺ helper T-lymphocyte subsets. To elucidate the role of L3T4⁺ T-lymphocytes in the development of insulitis and diabetes in NOD mice, we treated the animals with injections of monoclonal anti-L3T4 antibody. Administration of this antibody prevented the insulitis and diabetes in NOD mice. These results lead to conclusions that the L3T4⁺ helper T-lymphocytes may play an essential role in the pathogenesis of type I diabetes and that the manipulation of the OKT4⁺ (Leu3⁺) T-lymphocyte subset, the human homology of L3T4, with monoclonal antibodies may provide effective therapy for human type I diabetes.