Immunohistochemical characterization of monocytes-macrophages and dendritic cells involved in the initiation of the insulitis and beta-cell destruction in NOD mice.
This immunohistochemical study describes the infiltration pattern of monocytes-macrophages and dendritic cells during the development of insulitis and diabetes in the NOD mouse. A panel of monoclonal antibodies (MoAbs) was used to analyze pancreases of nondiabetic (glucosuria negative) male and female NOD mice at 3, 7, 10, and 17 weeks of age. BALB/c female mice 17-weeks-old, diabetic NOD female mice 20- to 30-weeks-old, and nondiabetic NOD male mice 22-weeks-old were used as controls. Three MoAbs (viz., ER-MP23, MOMA1, and BM8) were special and appeared to identify macrophage/dendritic cell subsets that either had a characteristic infiltration pattern in the initial phases of the autoimmune reaction before T-cell infiltration or were typical for the later beta-cell destructive insulitis process. 1) Raised numbers of ER-MP23+ and MOMA-1+ dendritic cells/macrophages were characteristic for the initial phases of the NOD insulitis in 3-week-old mice. The cells were found in and near swollen para-insular vessels. In 7-week-old mice, these ER-MP23+ and MOMA-1+ cells had accumulated around the islets and were the first hematopoietic cells detectable at these spots. 2) From 7 weeks of age onward, BM8+ macrophages could be found in the para- and peri-insulitis processes. However, only in females were these BM8+ macrophages found to infiltrate into the islets. In lymphoid tissues, ER-MP23 predominantly reacts with macrophages/dendritic cells present in the subcapsular and interfollicular sinuses of lymph nodes and the T-cell zones of these lymph nodes. ER-MP23 also reacts with tissue macrophages/dendritic cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Jansen
A
A
Department of Immunology, Erasmus University, Rotterdam, The Netherlands.
Homo-Delarche
F
F
Hooijkaas
H
H
Leenen
P J
PJ
Dardenne
M
M
Drexhage
H A
HA
D000818:Animals; D000911:Antibodies, Monoclonal; D000941:Antigens / Q000032:analysis; D003713:Dendritic Cells / Q000473:pathology*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D007515:Islets of Langerhans / Q000473:pathology*; D008264:Macrophages / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D009000:Monocytes / Q000473:pathology*; D010182:Pancreatic Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology*
D000911:Antibodies, Monoclonal; D000941:Antigens