Department of Pediatrics, Division of Immunology; Program in Molecular Medicine
Medical Subject Headings
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.
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.