Department of Pediatrics, Division of Immunology; Program in Molecular Medicine
Antigens, CD; Apoptosis Regulatory Proteins; CD8-Positive T-Lymphocytes; Cells, Cultured; Gene Expression; Herpesvirus 4, Human; Humans; Infectious Mononucleosis; Programmed Cell Death 1 Receptor; Receptors, Antigen, T-Cell; Up-Regulation
Immunology and Infectious Disease | Virology
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.
METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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.
Rights and Permissions
Copyright 2010 Greenough et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
PLoS One. 2010 Sep 23;5(9):e12926. doi: 10.1371/journal.pone.0012926. Link to article on publisher's site
Greenough, Thomas C.; Campellone, Shalyn C.; Brody, Robin M.; Jain, Surbhi; Sanchez-Merino, Victor; Somasundaran, Mohan; and Luzuriaga, Katherine, "Programmed Death-1 expression on Epstein Barr virus specific CD8+ T cells varies by stage of infection, epitope specificity, and T-cell receptor usage" (2010). Pediatric Publications and Presentations. 33.