title: Programmed Death-1 expression on Epstein Barr virus specific CD8+ T cells varies by stage of infection, epitope specificity, and T-cell receptor usage.
abstract: BACKGROUND
  Programmed Death-1 (PD-1) is an inhibitory member of the CD28 family of molecules expressed on CD8+ T cells in response to antigenic stimulation. To better understand the role of PD-1 in antiviral immunity we examined the expression of PD-1 on Epstein-Barr virus (EBV) epitope-specific CD8+ T cells during acute infectious mononucleosis (AIM) and convalescence.
  
  
  RESULTS
  Using flow cytometry, we observed higher frequencies of EBV-specific CD8+ T cells and higher intensity of PD-1 expression on EBV-specific CD8+ T cells during AIM than during convalescence. PD-1 expression during AIM directly correlated with viral load and with the subsequent degree of CD8+ T cell contraction in convalescence. Consistent differences in PD-1 expression were observed between CD8+ T cells with specificity for two different EBV lytic antigen epitopes. Similar differences were observed in the degree to which PD-1 was upregulated on these epitope-specific CD8+ T cells following peptide stimulation in vitro. EBV epitope-specific CD8+ T cell proliferative responses to peptide stimulation were diminished during AIM regardless of PD-1 expression and were unaffected by blocking PD-1 interactions with PD-L1. Significant variability in PD-1 expression was observed on EBV epitope-specific CD8+ T cell subsets defined by V-beta usage.
  
  
  CONCLUSIONS
  These observations suggest that PD-1 expression is not only dependent on the degree of antigen presentation, but also on undefined characteristics of the responding cell that segregate with epitope specificity and V-beta usage.
authors.affiliation: Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America. thomas.greenough@umassmed.edu
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Greenough
authors.forename: Shalyn C
authors.initials: SC
authors.lastname: Campellone
authors.forename: Robin
authors.initials: R
authors.lastname: Brody
authors.forename: Surbhi
authors.initials: S
authors.lastname: Jain
authors.forename: Victor
authors.initials: V
authors.lastname: Sanchez-Merino
authors.forename: Mohan
authors.initials: M
authors.lastname: Somasundaran
authors.forename: Katherine
authors.initials: K
authors.lastname: Luzuriaga
mesh_terms: D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002478:Cells, Cultured; D015870:Gene Expression; D004854:Herpesvirus 4, Human / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007244:Infectious Mononucleosis / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D061026:Programmed Cell Death 1 Receptor; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011948:Receptors, Antigen, T-Cell