title: Local expression of TNFalpha in neonatal NOD mice promotes diabetes by enhancing presentation of islet antigens.
abstract: The relationship of inflammation to autoimmunity has been long observed, but the underlying mechanisms are unclear. Here, we demonstrate that islet-specific expression of TNFalpha in neonatal nonobese diabetic mice accelerated diabetes. In neonatal transgenic mice, disease was preceded by apoptosis of some beta cells, upregulation of MHC class I molecules on residual islet cells, and influx and activation of both antigen-presenting cells bearing MHC-islet peptide complexes and T cells. Infiltrating dendritic cells/macrophages, but not B cells, from neonatal islets activated islet-specific T cells in vitro. Thus, inflammation can trigger autoimmunity by recruiting and activating dendritic cells/macrophages to present self-antigens to autoreactive T cells.
authors.affiliation: Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Green
authors.forename: E E
authors.initials: EE
authors.lastname: Eynon
authors.forename: R A
authors.initials: RA
authors.lastname: Flavell
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D017209:Apoptosis / Q000502:physiology; D001324:Autoantigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D007515:Islets of Langerhans / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019076:Transgenes; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D001324:Autoantigens; D014409:Tumor Necrosis Factor-alpha