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

Pa T. Ngom, Juan Solon, Sophie E. Moore, Gareth Morgan, Andrew M. Prentice, Richard Aspinall

Research output: Contribution to journalArticle

15 Citations (Scopus)
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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, 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.

Original languageEnglish
Article number41
JournalJournal of Biomedical Science
Volume18
Issue number1
Publication statusPublished - 15 Jun 2011
Externally publishedYes

Bibliographical note

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Keywords

  • Telomere Length
  • Cell Subset
  • Early Life Stressor
  • Relative Telomere Length
  • Thymic Function

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Pharmacology (medical)

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