title: 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.
abstract: 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.
authors.affiliation: Department of Immunology.
authors.forename: Diana
authors.initials: D
authors.lastname: van den Heuvel
authors.affiliation: Department of The Generation R Study Group, Erasmus MC, University Medical Center Department of Pediatrics, Erasmus MC-Sophia, Rotterdam.
authors.forename: Michelle A E
authors.initials: MA
authors.lastname: Jansen
authors.affiliation: Department of Immunology.
authors.forename: Wim A
authors.initials: WA
authors.lastname: Dik
authors.affiliation: Department of Immunology.
authors.forename: Halima
authors.initials: H
authors.lastname: Bouallouch-Charif
authors.affiliation: Department of Immunology.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Immunology.
authors.forename: Kevin A M
authors.initials: KA
authors.lastname: van Kester
authors.affiliation: Department of Immunology.
authors.forename: Marja A W
authors.initials: MA
authors.lastname: Smits-te Nijenhuis
authors.affiliation: Department of Immunology.
authors.forename: Marion J
authors.initials: MJ
authors.lastname: Kolijn-Couwenberg
authors.affiliation: Department of Epidemiology Department of The Generation R Study Group, Erasmus MC, University Medical Center Department of Pediatrics, Erasmus MC-Sophia, Rotterdam.
authors.forename: Vincent W V
authors.initials: VW
authors.lastname: Jaddoe
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands.
authors.forename: Ramon
authors.initials: R
authors.lastname: Arens
authors.affiliation: Department of Immunology.
authors.forename: Jacques J M
authors.initials: JJ
authors.lastname: van Dongen
authors.affiliation: Department of Pediatrics, Erasmus MC-Sophia, Rotterdam.
authors.forename: Henriëtte A
authors.initials: HA
authors.lastname: Moll
authors.affiliation: Department of Immunology.
authors.forename: Menno C
authors.initials: MC
authors.lastname: van Zelm
mesh_terms: D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000502:physiology*; D018259:Herpesvirus 1, Human / Q000276:immunology; D014645:Herpesvirus 3, Human / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D008457:Measles / Q000517:prevention & control; D008458:Measles Vaccine / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000502:physiology*; D013742:Tetanus / Q000517:prevention & control; D013743:Tetanus Antitoxin / Q000276:immunology*; D014611:Vaccination
chemical_list: D008458:Measles Vaccine; D013743:Tetanus Antitoxin
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)