Characterization of pancreatic islet cell infiltrates in NOD mice: effect of cell transfer and transgene expression.
Insulin-dependent diabetes mellitus can be transferred into young irradiated non-obese diabetic (NOD) mice by spleen cells from a diabetic NOD donor. T cells (both L3T4+ and Ly-2+) enter the pancreas 2 weeks following transfer. They are present initially at peri-islet locations but progressively infiltrate the islet with accompanying beta cell destruction. The infiltrate is heterogeneous with respect to V beta usage. Inflammatory macrophages (Mac-1+, F4/80+) can be detected at peri-islet locations at 1 week after transfer and continue to be recruited during the disease process. Their presence at the initiation of disease suggests that their primary function may be autoantigen presentation. Increased expression of major histocompatibility complex (MHC) class I molecules is observed on both endocrine and exocrine tissue in areas of intra-islet infiltration. MHC class II and ICAM-1 expression was restricted to the cells constituting the inflammatory infiltrate. Expression of these molecules was not observed on beta cells implying that presentation of autoantigen by the beta cell itself does not play a role in the beta cell destruction in NOD mice.
University College and Middlesex, School of Medicine, London, GB.
L A
LA
O'Reilly
P R
PR
Hutchings
P R
PR
Crocker
E
E
Simpson
T
T
Lund
D
D
Kioussis
F
F
Takei
J
J
Baird
A
A
Cooke
D000818:Animals; D001327:Autoimmune Diseases / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology*; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D016219:Immunotherapy, Adoptive; D018799:Intercellular Adhesion Molecule-1; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology*; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000473:pathology
D015815:Cell Adhesion Molecules; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D018799:Intercellular Adhesion Molecule-1