Dendritic cell apoptosis in the maintenance of immune tolerance

Science. 2006 Feb 24;311(5764):1160-4. doi: 10.1126/science.1122545.


Apoptosis in the immune system is critical for maintaining self-tolerance and preventing autoimmunity. Nevertheless, inhibiting apoptosis in lymphocytes is not alone sufficient to break self-tolerance, suggesting the involvement of other cell types. We investigated whether apoptosis in dendritic cells (DCs) helps regulate self-tolerance by generating transgenic mice expressing the baculoviral caspase inhibitor, p35, in DCs (DC-p35). DC-p35 mice displayed defective DC apoptosis, resulting in their accumulation and, in turn, chronic lymphocyte activation and systemic autoimmune manifestations. The observation that a defect in DC apoptosis can independently lead to autoimmunity is consistent with a central role for these cells in maintaining immune self-tolerance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Aging
  • Animals
  • Antibodies, Antinuclear / analysis
  • Apoptosis*
  • Autoimmunity*
  • B-Lymphocytes / immunology
  • Caspase Inhibitors
  • Cell Survival
  • Dendritic Cells / immunology*
  • Dendritic Cells / physiology*
  • Kidney / immunology
  • Lung / immunology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Self Tolerance*
  • Spleen / immunology
  • T-Lymphocytes / immunology
  • Viral Proteins / genetics
  • Viral Proteins / metabolism


  • Antibodies, Antinuclear
  • Caspase Inhibitors
  • Viral Proteins
  • p35 protein, Baculovirus