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


Ngom, PT; Solon, J; Moore, SE; Morgan, G; Prentice, AM; Aspinall, R; (2011) Thymic function and T cell parameters in a natural human experimental model of seasonal infectious diseases and nutritional burden. Journal of biomedical science, 18. ISSN 1021-7770 DOI: https://doi.org/10.1186/1423-0127-18-41

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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 beta 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 beta repertoire skewing was observed with 'public' expressions and deletions seen in TCRV beta 12/22 and TCRV beta 24, 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.

Item Type: Article
Keywords: b-virus-infection, hepatitis-b, plasmodium-falciparum, cytomegalovirus-infection, peripheral-blood, gambian mothers, guinea-bissau, hiv-infection, west-africa, breast-milk
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Population Health (2012- ) > Dept of Nutrition and Public Health Interventions Research (2003-2012)
Faculty of Epidemiology and Population Health > Dept of Population Health (2012- )
Research Centre: Centre for Global Non-Communicable Diseases (NCDs)
PubMed ID: 21676219
Web of Science ID: 292316700001
URI: http://researchonline.lshtm.ac.uk/id/eprint/366

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