Thymic function and T cell parameters in a natural human experimental model of seasonal infectious diseases and nutritional burden

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, TCRV 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⁺ TCRV repertoire skewing was observed with 'public' expressions and deletions seen in TCRV12/22 and TCRV24, 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.