PD-1 signalling in CD4(+) T cells restrains their clonal expansion to an immunogenic stimulus, but is not critically required for peptide-induced tolerance

Immunology. 2010 May;130(1):92-102. doi: 10.1111/j.1365-2567.2009.03216.x. Epub 2010 Jan 27.


The ultimate outcome of T-cell recognition of peptide-major histocompatibility complex (MHC) complexes is determined by the molecular context in which antigen presentation is provided. The paradigm is that, after exposure to peptides presented by steady-state dendritic cells (DCs), inhibitory signals dominate, leading to the deletion and/or functional inactivation of antigen-reactive T cells. This has been utilized in a variety of models providing peptide antigen in soluble form in the absence of adjuvant. A co-inhibitory molecule of considerable current interest is PD-1. Here we show that there is the opportunity for the PD-1/PD-L1 interaction to function in inhibiting the T-cell response during tolerance induction. Using traceable CD4(+) T-cell receptor (TCR) transgenic cells, together with a blocking antibody to disrupt PD-1 signalling, we explored the roles of PD-1 in the induction of tolerance versus a productive immune response. Intact PD-1 signalling played a role in limiting the extent of CD4(+) T-cell accumulation in response to an immunogenic stimulus. However, PD-1 signalling was not required for either the induction, or the maintenance, of peptide-induced tolerance; a conclusion underlined by successful tolerance induction in TCR transgenic cells genetically deficient for PD-1. These observations contrast with the reported requirement for PD-1 signals in CD8(+) T-cell tolerance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Separation
  • Flow Cytometry
  • Immune Tolerance / immunology*
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Ovalbumin / immunology
  • Peptide Fragments / immunology
  • Phenotype
  • Programmed Cell Death 1 Receptor
  • Signal Transduction / immunology*


  • Antigens, Differentiation
  • Pdcd1 protein, mouse
  • Peptide Fragments
  • Programmed Cell Death 1 Receptor
  • ovalbumin (325-339)
  • Ovalbumin