The PD-1-PD-L pathway in immunological tolerance

Trends Immunol. 2006 Apr;27(4):195-201. doi: 10.1016/ Epub 2006 Feb 24.


Since the first observation of spontaneous autoimmune diseases in programmed cell death 1 (PD-1) knockout mice, PD-1 has been postulated to have essential roles in the regulation of autoimmunity but the precise mechanism was largely unknown. Recent studies clearly demonstrated that PD-1 has dual roles in immunological tolerance: induction and maintenance of peripheral tolerance. PD-1 ligands (PD-Ls) on antigen-presenting cells have been shown to switch off autoreactive T cells and induce peripheral tolerance, whereas those on parenchymal cells prevent tissue destruction by suppressing effector T cells to maintain tolerance. In addition, PD-1 and other immuno-inhibitory receptors have been shown to collaborate in the regulation of tolerance. Here, we review recent studies on the role of PD-1 in immunological tolerance and discuss possible clinical applications of PD-1 manipulation.

Publication types

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

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • Apoptosis Regulatory Proteins / deficiency
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / immunology*
  • Apoptosis Regulatory Proteins / metabolism
  • Humans
  • Immune Tolerance / immunology*
  • Ligands
  • Signal Transduction*
  • T-Lymphocytes / immunology


  • Apoptosis Regulatory Proteins
  • Ligands