Abnormalities in dendritic cell and macrophage accumulation in the pancreas of nonobese diabetic (NOD) mice during the early neonatal period

Abstract

Dendritic cell (DC), macrophage (Mø) and l y m p h o cyte infiltrations have been observed in normal human perinatal pancreata, but have never been investigated so early in control mice. In type 1 diabetesprone NOD mice, these cells are thought to infiltrate first the periphery of the islets of Langerhans around weaning before further islet infiltration and ß-cell destruction. We quantified, during the first month of life, the numbers of DC (characterized by CD11c positivity and dendritic morphology), histiocyte-like Mø (characterized by ER-MP23 positivity) and Mø with scave n g i n g potential (characterized by BM8 positivity) in C57BL/6, DBA/2 and BALB/c control, and NOD and lymphocytedeficient NODscid mouse pancreata. First, CD11c+ DC were present at low densities from birth onwards in control pancreata, while densities were higher in NOD and NODscid. Second, high numbers of BM8+ and ER-MP23+ Mø were observed at birth in all strains investigated. After birth, particularly BM8+ cells disappeared progressively in control strains, but not in NOD and NODs c i d. Third, NOD mice also had more E R - M P 2 3+ Mø at birth compared to controls. Finally, DC and Mø localizations were similar in all strains, i.e., mostly as dispersed cells in periva s c u l a r, periductular, peri-islet areas and interlobular septa. The most remarkable finding was that particularly BM8+ Mø, were seen at sites of islet neogenesis and predominantly at the duct-islet interface. Our data showed that different types of APC were present in the pancreas during postnatal development in various control mouse strains and some differences were o b s e r ved in NOD and NOD s c i d mice from birth onwards.