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

Diana Van Den Heuvel, Michelle A E Jansen, Wim A. Dik, Halima Bouallouch-Charif, Dan Zhao, Kevin A M Van Kester, Marja A W Smits-Te Nijenhuis, Marion J. Kolijn-Couwenberg, Vincent W V Jaddoe, Ramon Arens, Jacques J M Van Dongen, Henriëtte A. Moll, Menno C. Van Zelm

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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.

Original languageEnglish
Pages (from-to)233-242
Number of pages10
JournalJournal of Infectious Diseases
Issue number2
Publication statusPublished - 15 Jan 2016
Externally publishedYes


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

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