Activation drives PD-1 expression during vaccine-specific proliferation and following lentiviral infection in macaques.
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.
Hokey
David A
DA
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Johnson
F Brad
FB
Smith
Jasmine
J
Weber
Joshua L
JL
Yan
Jian
J
Hirao
Lauren
L
Boyer
Jean D
JD
Lewis
Mark G
MG
Makedonas
George
G
Betts
Michael R
MR
Weiner
David B
DB
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
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