Islet abnormalities associated with an early influx of dendritic cells and macrophages in NOD and NODscid mice.
In the nonobese diabetic (NOD) mouse model for type 1 diabetes, the inflammatory infiltration of islets starts with an influx of dendritic cells (DC) and macrophages (Mphi) at approximately 4 weeks of age. Around this time, NOD mice show endocrine abnormalities, indicated by a transient hyperinsulinemia that lasts until 8 weeks of age. Subsequently, they develop abnormally large islets of Langerhans, here designated as "mega-islets." NODscid mice, which lack functional lymphocytes, also exhibit transient hyperinsulinemia, but to a lesser extent. First, to determine the role of lymphocytes in the morphological islet abnormalities, we compared 6-week-old (prediabetic) NOD and NODscid females regarding mega-islet development and accumulation of antigen-presenting cells (APC), particularly CD11c+ DC and ERMP23+ Mphi. In NODscid mice, early APC infiltration and mega-islets were present, but less marked compared with NOD mice, thus suggesting a role of lymphocytes in mega-islet formation. In both NOD and NODscid mice, the APC infiltration was predominantly found around the mega-islets, suggesting a relationship between both parameters. Second, to analyze the role of beta-cell hyperactivity in mega-islet formation, we studied the effect of short-term prophylactic insulin treatment on these parameters. Prophylactic insulin treatment decreased the percentages of mega-islets in both NOD and NODscid mice, indicating that beta-cell hyperactivity is also involved in mega-islet formation. In conclusion, mega-islet formation in mice with the NOD genetic background takes place under the influence of both beta-cell hyperactivity and leukocytes.
Rosmalen
J G
JG
Department of Immunology, Erasmus University, Rotterdam, The Netherlands. rosmalen@immu.fgg.eur.nl
Homo-Delarche
F
F
Durant
S
S
Kap
M
M
Leenen
P J
PJ
Drexhage
H A
HA
D000818:Animals; D002465:Cell Movement; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D007328:Insulin / Q000494:pharmacology; D007515:Islets of Langerhans / Q000473:pathology*; D008214:Lymphocytes / Q000502:physiology; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID
D007328:Insulin