title: Thymic function and T cell parameters in a natural human experimental model of seasonal infectious diseases and nutritional burden.
abstract: BACKGROUND
  The study exploits a natural human experimental model of subsistence farmers experiencing chronic and seasonally modified food shortages and infectious burden. Two seasons existed, one of increased deprivation and infections (Jul-Dec), another of abundance and low infections (Jan-Jun); referred to as the hungry/high infection and harvest/low infection seasons respectively. Prior analysis showed a 10-fold excess in infectious disease associated mortality in young adults born in the hungry/high infection versus harvest/low infection season, and reduced thymic output and T cell counts in infancy. Here we report findings on the role of early life stressors as contributors to the onset of T cell immunological defects in later life.
  
  
  METHODS
  We hypothesised that season of birth effects on thymic function and T cell immunity would be detectable in young adults since Kaplan-Meier survival curves indicated this to be the time of greatest mortality divergence. T cell subset analyses by flow-cytometry, sjTRECs, TCRVβ repertoire and telomere length by PCR, were performed on samples from 60 males (18-23 y) selected to represent births in the hungry/high infection and harvest/low infection
  
  
  RESULTS
  Total lymphocyte counts were normal and did not differ by birth season. CD3+ and CD4+ but not CD8+ counts were lower for those born during the hungry/high infection season. CD8+ telomere length also tended to be shorter. Overall, CD8+ TCRVβ repertoire skewing was observed with 'public' expressions and deletions seen in TCRVβ12/22 and TCRVβ24, respectively but no apparent effect of birth season.
  
  
  CONCLUSIONS
  We conclude that, although thymic function was unchanged, the CD4+ and CD3+ counts, and CD8+ telomere length results suggested that aspects of adult T cell immunity were under the influence of early life stressors. The endemicity of CMV and HBV suggested that chronic infections may modulate immunity through T cell repertoire development. The overall implications being that, this population is at an elevated risk of premature immunosenescence possibly driven by a combination of nutritional and infectious burden.
authors.affiliation: Nutrition Programme, MRC Laboratories, The Gambia. tngom@mrc.gm
authors.forename: Pa T
authors.initials: PT
authors.lastname: Ngom
authors.forename: Juan
authors.initials: J
authors.lastname: Solon
authors.forename: Sophie E
authors.initials: SE
authors.lastname: Moore
authors.forename: Gareth
authors.initials: G
authors.lastname: Morgan
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Prentice
authors.forename: Richard
authors.initials: R
authors.lastname: Aspinall
mesh_terms: D000293:Adolescent; D001724:Birth Weight; D015331:Cohort Studies; D003141:Communicable Diseases / Q000453:epidemiology; D005434:Flow Cytometry; D005714:Gambia / Q000453:epidemiology; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D044342:Malnutrition / Q000276:immunology*; D011446:Prospective Studies; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D012621:Seasons; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*; D055815:Young Adult
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta