Local expression of TNFalpha in neonatal NOD mice promotes diabetes by enhancing presentation of islet antigens |
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Authors: | EA Green EE Eynon RA Flavell |
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Affiliation: | Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. |
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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. |
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