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

Immunity. 1998 Nov;9(5):733-43. doi: 10.1016/s1074-7613(00)80670-6.


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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen Presentation / immunology*
  • Apoptosis / physiology
  • Autoantigens / immunology*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / metabolism*
  • Diabetes Mellitus, Type 1 / pathology
  • Disease Progression
  • Female
  • Islets of Langerhans / immunology*
  • Islets of Langerhans / metabolism*
  • Islets of Langerhans / pathology
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Mice, Transgenic
  • Sensitivity and Specificity
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Transgenes
  • Tumor Necrosis Factor-alpha / biosynthesis*


  • Autoantigens
  • Tumor Necrosis Factor-alpha