Developmentally regulated expression of the PD-1 protein on the surface of double-negative (CD4-CD8-) thymocytes

Int Immunol. 1996 May;8(5):773-80. doi: 10.1093/intimm/8.5.773.


PD-1, a member of the Ig superfamily, was previously isolated from an apoptosis-induced T cell hybridoma 2B4.11 by subtractive hybridization. Expresson of the PD-1 mRNA is restricted to thymus in adult mice. Using an anti-PD-1 mAb (J43), we examined expression of the PD-1 protein during differentiation of thymocytes in normal adult, fetal and RAG-2(-/-) mice with or without anti-CD3 mAb stimulation. While PD-1 was expressed only on 3-5% of total normal thymocytes, approximately 34% of the CD4(-)CD8(-) double-negative (DN) fraction are PD-1(+) cells with two distinct expression levels (low and high). PD-1(high) thymocytes belonged to TCR gammadelta lineage cells. In the DN compartment of the TCR alphabeta lineage, PD-1 expression started at the low level from the CD44(+)CD25(+) stage and the majority of thymocytes expressed PD-1 at the CD44(-)CD25(-) stage in which the thymocytes express TCR beta chains. The anti-CD3epsilon antibody administration augmented the PD-1 expression as well as the differentiation of the CD44(-)CD25(+) DN cells into the CD44(-)CD25(-) DN stage, not only in normal mice but also in RAG-2-deficient mice. The fraction of the PD-1(low) cells in the CD4(+)CD8(+) double-positive (DP) compartment was very small (<5%) but increased by stimulation with the anti-CD3 antibody, although the total number of DP cells was drastically reduced. The results show that PD-1 expression is specifically induced at the stages preceding clonal selection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / immunology*
  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antigens, Surface / biosynthesis*
  • Apoptosis Regulatory Proteins
  • CD3 Complex / immunology
  • CD4 Antigens / physiology*
  • CD8 Antigens / physiology*
  • Cell Differentiation / immunology
  • DNA-Binding Proteins*
  • Female
  • Hyaluronan Receptors / immunology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Programmed Cell Death 1 Receptor
  • Proteins / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • Receptors, Interleukin-2 / immunology
  • T-Lymphocyte Subsets / classification*
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / metabolism
  • Thymus Gland / cytology
  • Thymus Gland / growth & development*
  • Thymus Gland / metabolism*


  • Antibodies, Monoclonal
  • Antigens, Surface
  • Apoptosis Regulatory Proteins
  • CD3 Complex
  • CD4 Antigens
  • CD8 Antigens
  • DNA-Binding Proteins
  • Hyaluronan Receptors
  • Neoplasm Proteins
  • Pdcd1 protein, mouse
  • Programmed Cell Death 1 Receptor
  • Proteins
  • Rag2 protein, mouse
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Interleukin-2
  • V(D)J recombination activating protein 2