The role of the PD-1 pathway in autoimmunity and peripheral tolerance

Brian T. Fife, Kristen E. Pauken

Research output: Contribution to journalArticlepeer-review

280 Scopus citations


Programmed death-1 (PD-1) is a surface receptor critical for the regulation of T cell function during immunity and tolerance. PD-1 interactions with its ligands PD-L1 and PD-L2 inhibit T cell effector functions in an antigen-specific manner. This paper examines the role of PD-1 in limiting autoreactivity and establishing self-tolerance and discusses the hypothesis that PD-1 ligand (PD-L) expression both spatially and temporally dictates the fate of self-reactive T cells during the breakdown of peripheral tolerance and development of autoimmunity. We focus our discussion on the role of PD-1/PD-L interactions during peripheral tolerance, the differential role for PD-L1 and PD-L2 in response to environmental or self-antigens, and the impact of PD-1 signaling on dynamic T cell motility and the T cell receptor (TCR) stop signal. Finally, we discuss the potential to selectively target the PD-1 pathway therapeutically to alter T cell function during autoimmunity.

Original languageEnglish (US)
Pages (from-to)45-59
Number of pages15
JournalAnnals of the New York Academy of Sciences
Issue number1
StatePublished - Jan 2011


  • Autoimmune
  • Diabetes
  • PD-1
  • T cell
  • Tolerance


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