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Long-term effects of perinatal nutrition on T lymphocyte kinetics in young Gambian men^1,2,3

¹ From the Centre for Infection, St George’s, University of London, London, United Kingdom (HG, YZ, GEG, and DCM); the MRC International Nutrition Group, London School of Hygiene and Tropical Medicine, London, United Kingdom (HG, JAS, and AMP); the Edward Jenner Institute for Vaccine Research, Compton, United Kingdom (DLW); the Medical Research Council Keneba, Keneba, Gambia (JAS, PTN, and AMP); the Department of Immunology and Molecular Pathology, University College London, London, United Kingdom (SMH); the Department of Immunology, Imperial College London, London, United Kingdom (PTN and RA); and the Clinical School, University of Wales, Swansea, United Kindgom (GM)

Background: Nutritional status is highly dependent on season in countries such as The Gambia. In a rural Gambian setting, individuals born during periods of seasonal nutritional deprivation ("hungry seasons") are susceptible to mortality from infectious diseases in adult life.

Objective: We investigated the hypothesis that impaired immunocompetence in those born in the hungry season results from an underlying defect in immunologic memory, similar to the immunosenescence of old age, which is likely to be reflected in the phenotype and kinetics of T lymphocytes in young adults.

Design: T cell phenotype in terms of CD3, CD4, CD8, CD45RA, and CD45R0 expression and in vivo dynamics measured by stable isotope labeling of T cell subsets combined with gas chromatography–mass spectrometry and frequency of T cell receptor excision circles were measured in 25 young (18–24-y-old) Gambian men. Thirteen of these 25 men were exposed to perinatal malnutrition as defined by birth season and birth weight.

Results: In persons born in the hungry season with low birth weight, no differences in the proportions of memory or naive T cells were found. Kinetic analysis showed higher proliferation rates in memory (CD45R0⁺) subsets of T cells than in naïve (CD45R0^–) cells, which is consistent with previous studies, but no evidence was found for an effect of birth weight or season on T lymphocyte proliferation and disappearance rates. No significant correlations were found between in vivo T cell kinetics and frequency of T cell receptor excision circles. Only absolute numbers of granulocytes were elevated in those born in the nutritionally deprived season.

Conclusion: In healthy young Gambian men, T lymphocyte homeostasis is extremely robust regardless of perinatal nutritional compromise.

Key Words: Nutritional programming • T cell kinetics • lymphocytes • Gambia • stable isotopes