Dendritic cells and macrophages are essential for the retention of lymphocytes in (peri)-insulitis of the nonobese diabetic mouse: A phagocyte depletion study

Abstract

Dendritic cells (DC) and macrophages (Mφ) are present in high numbers in the pancreas of the non-obese diabetic (NOD) mouse during the diabetogenic process from very early stages onwards. In this study, we used clodronate-loaded liposomes to mediate the temporary systemic depletion of these phagocytic cells and monocytic precursors in order to modulate the pancreatic inflammation. Two intraperitoneal injections given with a 2-day interval to 8-week-old NOD mice depleted monocytes from the circulation and monocytes, DC and Mφ from the spleen within the first days after the injections. Monocytes, DC and Mφ reappeared in the circulation and the spleen within one week and had an unchanged phenotype and antigen presenting function. Interestingly, this treatment caused a delayed disappearance (7-21 days postinjection) of DC and Mφ from the endocrine pancreas at a time when monocytes, DC and Mφ had already repopulated the circulation and the spleen. The depletion of DC and Mφ from the endocrine pancreas was accompanied by a total disappearance of lymphocytes from the pancreas. DC, Mφ and lymphocytes reappeared in the pancreatic inflammatory infiltrates in treated mice from 28 days postdepletion onwards. Importantly, the treatment significantly postponed the onset of diabetes, leading to a strongly decreased incidence by 35 weeks of age. Taken together, our data show an essential role of phagocytic cells, that is, DC and Mφ, in the recruitment of lymphocytes to the pancreatic islets in NOD mice. © 2005 USCAP, Inc All rights reserved.