Cytomegalovirus- and Epstein-Barr Virus-Induced T-Cell Expansions in Young Children Do Not Impair Naive T-cell Populations or Vaccination Responses: The Generation R Study

J Infect Dis. 2016 Jan 15;213(2):233-42. doi: 10.1093/infdis/jiv369. Epub 2015 Jul 3.


Background: Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) induce effector memory T-cell expansions, which are variable and potentially depend on the age at primary exposure and coinfections. We evaluated the T-cell compartment and herpesvirus infections in 6-year-old children.

Methods: T-cell subsets and immunoglobulin G seropositivity for CMV, EBV, herpes-simplex virus 1, and varicella-zoster virus were studied in 1079 6-year-old children. A random subgroup of 225 children was evaluated for CMV and EBV seropositivity before 2 years of age and for vaccination responses against measles and tetanus.

Results: CMV and EBV infections were associated with significant expansions of CD27(-) and CD27(+) effector memory T cells, respectively. These expansions were enhanced in CMV-EBV-coinfected children and were independent of varicella-zoster virus or herpes-simplex virus 1 coinfection. Naive and central memory T-cell numbers were not affected, nor were anti-tetanus and anti-measles immunoglobulin G levels. Children infected before 2 years of age showed smaller effector memory T-cell expansions than those infected between 2 and 6 years of age.

Conclusions: CMV- and EBV-related T-cell expansions do not impair naive T-cell numbers or maintenance of protective responses against nonrelated pathogens. Duration of infection was not directly related to larger expansions of effector memory T cells in children, suggesting that other mechanisms affect these expansions at later age.

Keywords: Epstein-Barr virus (EBV); T-cell compartment; childhood adaptive immune system; cytomegalovirus (CMV); effector memory T-cell expansions; herpes-simplex virus 1 (HSV-1); persistent herpesvirus infection; varicella-zoster virus (VZV).

Publication types

  • Clinical Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation
  • Child
  • Child, Preschool
  • Cytomegalovirus / physiology*
  • Herpesvirus 1, Human / immunology
  • Herpesvirus 3, Human / immunology
  • Herpesvirus 4, Human / physiology*
  • Humans
  • Measles / prevention & control
  • Measles Vaccine / immunology*
  • T-Lymphocyte Subsets / physiology*
  • Tetanus / prevention & control
  • Tetanus Antitoxin / immunology*
  • Vaccination


  • Measles Vaccine
  • Tetanus Antitoxin