title: Large scale analysis of pediatric antiviral CD8+ T cell populations reveals sustained, functional and mature responses.
abstract: BACKGROUND
  Cellular immunity plays a crucial role in cytomegalovirus (CMV) infection and substantial populations of CMV-specific T cells accumulate throughout life. However, although CMV infection occurs during childhood, relatively little is know about the typical quantity and quality of T cell responses in pediatric populations.
  
  
  METHODS
  One thousand and thirty-six people (Male/Female = 594/442, Age: 0-19 yr.; 959 subjects, 20-29 yr.; 77 subjects) were examined for HLA typing. All of 1036 subjects were tested for HLA-A2 antigen. Of 1036 subjects, 887 were also tested for HLA-A23, 24 antigens. In addition, 50 elderly people (Male/Female = 11/39, Age: 60-92 yr.) were also tested for HLA-A2 antigen. We analyzed the CD8+ T cell responses to CMV, comparing these to responses in children and young. The frequencies, phenotype and function CD8+ T cells for two imunodominant epitopes from pp65 were measured.
  
  
  RESULTS
  We observed consistently high frequency and phenotypically "mature" (CD27 low, CD28 low, CD45RA+) CMV-specific CD8+ T cell responses in children, including those studied in the first year of life. These CD8+ T cells retained functionality across all age groups, and showed evidence of memory "inflation" only in later adult life.
  
  
  CONCLUSIONS
  CMV consistently elicits a very strong CD8+ T cell response in infants and large pools of CMV specific CD8+ T cells are maintained throughout childhood. The presence of CMV may considerably mould the CD8+ T cell compartment over time, but the relative frequencies of CMV-specific cells do not show the evidence of a population-level increase during childhood and adulthood. This contrast with the marked expansion ("inflation") of such CD8+ T cells in older adults. This study indicates that large scale analysis of peptide specific T cell responses in infants is readily possible. The robust nature of the responses observed suggests vaccine strategies aimed at priming and boosting CD8+ T cells against major pathogens (including HIV, malaria and CMV itself) could be successful in this age-group.
authors.affiliation: Department of Pediatrics, National Defense Medical College, Saitama, Japan. haruki-komatsu@chive.ocn.ne.jp
authors.forename: Haruki
authors.initials: H
authors.lastname: Komatsu
authors.forename: Ayano
authors.initials: A
authors.lastname: Inui
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sogo
authors.forename: Tomoo
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Hironori
authors.initials: H
authors.lastname: Nagasaka
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Nonoyama
authors.forename: Sophie
authors.initials: S
authors.lastname: Sierro
authors.forename: John
authors.initials: J
authors.lastname: Northfield
authors.forename: Michaela
authors.initials: M
authors.lastname: Lucas
authors.forename: Anita
authors.initials: A
authors.lastname: Vargas
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman