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

Abstract

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.

• Authors: David A Hokey, F Brad Johnson, Jasmine Smith, Joshua L Weber, Jian Yan, Lauren Hirao, Jean D Boyer, Mark G Lewis, George Makedonas, Michael R Betts, David B Weiner
• Journal: European journal of immunology (Eur J Immunol) Vol. 38 Issue 5 Pg. 1435-45 (May 2008) ISSN: 0014-2980 [Print] Germany
• PMID: 18389475 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• 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

Topics

• Animals
• Antigens, Bacterial (immunology)
• Apoptosis Regulatory Proteins (metabolism)
• CD28 Antigens (analysis)
• CD3 Complex (analysis)
• CD4-Positive T-Lymphocytes (immunology, metabolism)
• CD8-Positive T-Lymphocytes (immunology, metabolism)
• Cell Proliferation
• Enterotoxins (immunology)
• Gene Products, env (immunology)
• Gene Products, pol (genetics, 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, immunology)
• T-Lymphocyte Subsets (immunology, metabolism)
• T-Lymphocytes (immunology, metabolism)
• Telomere (chemistry)
• Tumor Necrosis Factor-alpha (metabolism)
• Vaccines, DNA (immunology)
• fas Receptor (analysis)