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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigen Presentation / immunology*
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Apoptosis / physiology
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Autoantigens / immunology*
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Diabetes Mellitus, Type 1 / immunology*
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Diabetes Mellitus, Type 1 / metabolism*
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Diabetes Mellitus, Type 1 / pathology
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Disease Progression
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Female
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Islets of Langerhans / immunology*
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Islets of Langerhans / metabolism*
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Islets of Langerhans / pathology
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Lymphocyte Activation
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Male
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Mice
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Mice, Inbred NOD
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Mice, SCID
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Mice, Transgenic
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Sensitivity and Specificity
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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Transgenes
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Tumor Necrosis Factor-alpha / biosynthesis*
Substances
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Autoantigens
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Tumor Necrosis Factor-alpha