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 bu
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