title: 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.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Hokey
authors.forename: F Brad
authors.initials: FB
authors.lastname: Johnson
authors.forename: Jasmine
authors.initials: J
authors.lastname: Smith
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Weber
authors.forename: Jian
authors.initials: J
authors.lastname: Yan
authors.forename: Lauren
authors.initials: L
authors.lastname: Hirao
authors.forename: Jean D
authors.initials: JD
authors.lastname: Boyer
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lewis
authors.forename: George
authors.initials: G
authors.lastname: Makedonas
authors.forename: Michael R
authors.initials: MR
authors.lastname: Betts
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D018106:CD28 Antigens / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D004768:Enterotoxins / Q000276:immunology; D015686:Gene Products, env / Q000276:immunology; D015684:Gene Products, pol / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D008252:Macaca fascicularis; D008253:Macaca mulatta; D010446:Peptide Fragments / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D016615:Telomere / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019444:Vaccines, DNA / Q000276:immunology*; D019014:fas Receptor / Q000032:analysis
chemical_list: D000942:Antigens, Bacterial; D051017:Apoptosis Regulatory Proteins; D018106:CD28 Antigens; D017252:CD3 Complex; D004768:Enterotoxins; D015686:Gene Products, env; D015684:Gene Products, pol; D007376:Interleukin-2; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; D019444:Vaccines, DNA; D019014:fas Receptor; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma