In vivo evidence that L3T4 + T cells recruit Lyt-2 + T cells to mediate beta cell destruction in the autoimmune NOD mouse

Abstract

The loss of insulin-producing cells during the development of type 1 diabetes is dependent on leukocyte infiltration of β-islets in the pancreas. Injection of antibodies to integrins and their ligands has been shown to prevent the development of diabetes in non-obese diabetic (NOD) mice. However, little is known about the progression of infiltration by leukocytes after their homing and extravasation into the pancreas. In the present study, the effect of monoclonal antibodies (mAbs) to α4 andα5 integrins on leukocytes that had infiltrated the islets was characterized in NOD mice at 10 weeks of age when insulitis was in progress, or in mice with recent onset of diabetes. Injection of mAbs to either α4 orα5 integrins had little effect on the extent of leukocyte infiltration in 10-week-old or diabetic mice. In contrast, leukocyte infiltration was significantly reduced upon injection of mAbs to both α4 andα5 integrins. The reduction in leukocyte infiltration was due to decreases in the percentage of islets with intraislet infiltration. However, the observed effect of mAbs to α4 andα5 integrins was reversible, since intraislet infiltration resumed upon termination of antibody treatment. Results suggest that after homing to the pancreas, leukocytes utilize both α4 andα5 integrins for intraislet infiltration.