Macrophages, T cell receptor usage, and endothelial cell activation in the pancreas at the onset of insulin-dependent diabetes mellitus.
Current knowledge of the phenotype of mononuclear cells accumulating in pancreatic islets in insulin-dependent diabetes (IDDM) and factors determining their homing into the pancreas is limited. Therefore, a pancreas obtained at the onset of IDDM was studied in detail. Cryostat sections were stained for mononuclear cell types, T cell receptor subtypes, and adhesion molecules of vascular endothelium and studied by immunofluorescence microscopy, and peripheral blood mononuclear cells were phenotyped using flow cytometry. Monocytes/macrophages (lysozyme- or CD 14-reactive cells) were identified among other mononuclear cell types in islet infiltrates. V beta 8-positive T cells were overrepresented, but T cells with other V beta s studied (V beta 5, V beta 5.1, V beta 6, V beta 12) were also found. The vascular endothelium of the islets and many small vessels nearby islets strongly expressed intercellular adhesion molecule-1, whereas vascular cell adhesion molecule-1 and E-selectin were totally absent. We conclude: (a) that increased expression of intercellular adhesion molecule-1 on vascular endothelium may increase endothelial adhesion of mononuclear cells and enhance their accumulation in the pancreas during diabetic insulitis; (b) that T cells with certain T cell receptors can be enriched in infiltrated pancreatic islets; and (c) that macrophages and antigen-specific CD 8-positive T cells are involved in pancreatic beta cell destruction at the onset of IDDM.
Hänninen
A
A
Department of Pediatrics, University of Turku, Finland.
Jalkanen
S
S
Salmi
M
M
Toikkanen
S
S
Nikolakaros
G
G
Simell
O
O
D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D015815:Cell Adhesion Molecules / Q000032:analysis; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology*; D018950:Lipopolysaccharide Receptors; D008264:Macrophages / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*; D019010:Vascular Cell Adhesion Molecule-1
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015815:Cell Adhesion Molecules; D000949:Histocompatibility Antigens Class II; D018950:Lipopolysaccharide Receptors; D011948:Receptors, Antigen, T-Cell; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1