Local expression of TNFalpha in neonatal NOD mice promotes diabetes by enhancing presentation of islet antigens

E A Green, E E Eynon, R A Flavell

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)733-43
Number of pages11
JournalImmunity
Volume9
Issue number5
Publication statusPublished - 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

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