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.
Original language | English |
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Pages (from-to) | 733-43 |
Number of pages | 11 |
Journal | Immunity |
Volume | 9 |
Issue number | 5 |
Publication status | Published - 1998 |
Keywords
- Animals
- Antigen Presentation
- Apoptosis
- Autoantigens
- B-Lymphocytes
- Dendritic Cells
- Diabetes Mellitus, Type 1
- Disease Progression
- Female
- Islets of Langerhans
- Lymphocyte Activation
- Male
- Mice
- Mice, Inbred NOD
- Mice, SCID
- Mice, Transgenic
- Sensitivity and Specificity
- T-Lymphocytes
- Transgenes
- Tumor Necrosis Factor-alpha