Activation drives PD-1 expression during vaccine-specific proliferation and following lentiviral infection in macaques

Eur J Immunol. 2008 May;38(5):1435-45. doi: 10.1002/eji.200737857.


Recent data supports that increased expression of PD-1, a negative regulator of immune function, is associated with T cell exhaustion during chronic viral infection. However, PD-1 expression during acute infection and vaccination has not been studied in great detail in primates. Here, we examine PD-1 expression on CD3(+) T cells following DNA vaccination or lentiviral infection of macaques. Ex vivo peptide stimulation of PBMC from DNA-vaccinated uninfected macaques revealed a temporal increase in PD-1 expression in proliferating antigen-specific CD8(+) T cells. Following the initial increase, PD-1 expression steadily declined as proliferation continued, with a concomitant increase in IFN-gamma secretion. Subsequent examination of PD-1 expression on T cells from uninfected and lentivirus-infected non-vaccinated macaques revealed a significant increase in PD-1 expression with lentiviral infection, consistent with previous reports. PD-1 expression was highest on cells with activated memory and effector phenotypes. Despite their decreased telomere length, PD-1(hi) T cell populations do not appear to have statistically significant uncapped telomeres, typically indicative of proliferative exhaustion, suggesting a different mechanistic regulation of proliferation by PD-1. Our data indicate that PD-1 expression is increased as a result of T cell activation during a primary immune response as well as during persistent immune activation in macaques.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, Bacterial / immunology
  • Apoptosis Regulatory Proteins / metabolism*
  • CD28 Antigens / analysis
  • CD3 Complex / analysis
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Proliferation*
  • Enterotoxins / immunology
  • Gene Products, env / immunology
  • Gene Products, pol / genetics
  • Gene Products, pol / immunology
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism
  • Lymphocyte Activation / immunology*
  • Macaca fascicularis
  • Macaca mulatta
  • Peptide Fragments / immunology
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Immunodeficiency Virus / genetics
  • Simian Immunodeficiency Virus / immunology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Telomere / chemistry
  • Tumor Necrosis Factor-alpha / metabolism
  • Vaccines, DNA / immunology*
  • fas Receptor / analysis


  • Antigens, Bacterial
  • Apoptosis Regulatory Proteins
  • CD28 Antigens
  • CD3 Complex
  • Enterotoxins
  • Gene Products, env
  • Gene Products, pol
  • Interleukin-2
  • Peptide Fragments
  • Tumor Necrosis Factor-alpha
  • Vaccines, DNA
  • fas Receptor
  • enterotoxin B, staphylococcal
  • Interferon-gamma