Infection with cytomegalovirus but not herpes simplex virus induces the accumulation of late-differentiated CD4+ and CD8+ T-cells in humans

J Gen Virol. 2011 Dec;92(Pt 12):2746-2756. doi: 10.1099/vir.0.036004-0. Epub 2011 Aug 3.

Abstract

Human cytomegalovirus (CMV) establishes persistent, usually asymptomatic, infection in healthy people. Because CMV infection is associated with the presence of lower proportions of peripheral naïve CD8+ T-cells and a higher fraction of late-differentiated CD8+ cells, commonly taken as biomarkers of age-associated compromised adaptive immunity ('immunosenescence'), we asked whether chronic exposure to any persistent virus mediates these effects. Herpes simplex virus (HSV) is also a widespread herpesvirus that establishes lifelong persistence, but, unlike CMV, its impact on the distribution of T-cell subsets has not been established. Here, we analysed T-cell subsets in 93 healthy people aged 42-81 years infected or not infected with CMV and/or HSV. Individuals harbouring CMV were confirmed to possess lower frequencies of naïve CD8+ T-cells (defined as CD45RA+CCR7+CD27+CD28+) and greater proportions of late-differentiated effector memory (CD45RA-CCR7-CD27-CD28-) and so-called TEMRA (CD45RA+CCR7-CD27-CD28-) CD4 and CD8 subsets, independent of HSV seropositivity. In CMV-seronegative donors, HSV did not affect T-cell subset distribution significantly. We conclude that these hallmarks of age-associated alterations to immune signatures are indeed observed in the general population in people infected with CMV and not those infected with a different persistent herpesvirus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • CD28 Antigens / analysis
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / pathology
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / virology
  • Cell Differentiation
  • Cytomegalovirus / growth & development*
  • Cytomegalovirus Infections / immunology
  • Cytomegalovirus Infections / pathology
  • Female
  • Flow Cytometry
  • Humans
  • Leukocyte Common Antigens / analysis
  • Male
  • Middle Aged
  • Receptors, CCR7 / metabolism
  • Simplexvirus / growth & development*
  • T-Lymphocyte Subsets / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / analysis

Substances

  • CD28 Antigens
  • Receptors, CCR7
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Leukocyte Common Antigens