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    Programmed Death-1 expression on Epstein Barr virus specific CD8+ T cells varies by stage of infection, epitope specificity, and T-cell receptor usage

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    Authors
    Greenough, Thomas C.
    Campellone, Shalyn C.
    Brody, Robin M.
    Jain, Surbhi
    Sanchez-Merino, Victor
    Somasundaran, Mohan
    Luzuriaga, Katherine
    UMass Chan Affiliations
    Program in Molecular Medicine
    Department of Pediatrics, Division of Immunology
    Document Type
    Journal Article
    Publication Date
    2010-09-23
    Keywords
    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
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    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. 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.
    Source
    PLoS One. 2010 Sep 23;5(9):e12926. doi: 10.1371/journal.pone.0012926. Link to article on publisher's site
    DOI
    10.1371/journal.pone.0012926
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/43721
    PubMed ID
    20886079
    Related Resources
    Link to Article in PubMed
    Rights
    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.
    ae974a485f413a2113503eed53cd6c53
    10.1371/journal.pone.0012926
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