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

By P. T. Ngom, J. Solon, S. E. Moore, G. Morgan, A. M. Prentice and Richard Aspinall


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

Publisher: S. Karger AG / BioMed Central
Year: 2011
DOI identifier: 10.1186/1423-0127-18-41
OAI identifier:
Provided by: Cranfield CERES

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  1. (1994). A community study of T lymphocyte subsets and malaria parasitaemia. Trans R Soc Trop Med Hyg doi
  2. (1993). A malaria control trial using insecticidetreated bed nets and targeted chemoprophylaxis in a rural area of The Gambia, west Africa. 1. A review of the epidemiology and control of malaria in The Gambia, west Africa. Trans R Soc Trop Med Hyg doi
  3. (1999). A: Determinants of sustainable CD4 lymphocyte count increases in response to antiretroviral therapy. Aids doi
  4. (2007). A: Risk factors for and clinical outcome of congenital cytomegalovirus infection in a peri-urban WestAfrican birth cohort. PLoS One doi
  5. (2000). A: T cell receptor usage of virus-specific CD8 cells and recognition of viral mutations during acute and persistent hepatitis B virus infection. doi
  6. (2000). A: The role of virus-specific CD8(+) cells in liver damage and viral control during persistent hepatitis B virus infection. doi
  7. (1981). AA: Long-term energy balance in child-bearing Gambian women.
  8. (2006). Adewole TA: Plasma selenium concentration and glutathione peroxidase activity in HIV-1/AIDS infected patients: a correlation with the disease progression. Niger Postgrad Med J
  9. (1990). Allshire RC: Telomere reduction in human colorectal carcinoma and with ageing. Nature doi
  10. (1999). AM: Prenatal or early postnatal events predict infectious deaths in young adulthood in rural Africa.
  11. (2000). BD: In vivo reduction of telomere length in human antigen-reactive memory T cells. doi
  12. (2004). Belyakov IM: Cytokines in the thymus: production and biological effects. Curr Med Chem doi
  13. (2009). Camargo CA Jr: Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med doi
  14. (2009). Camargo CA Jr: Vitamin D, respiratory infections, and asthma. Curr Allergy Asthma Rep doi
  15. (2006). Carbone FR: CD4+ T cells can protect APC from CTL-mediated elimination. doi
  16. (1995). CB: Telomere shortening is associated with cell division in vitro and in vivo. Exp Cell Res doi
  17. (1994). Cole TJ: Seasonal changes in growth and energy status in the Third World. Proc Nutr Soc doi
  18. (1999). Contributions of CD4+, CD8+, and CD4+CD8+ T cells to skewing within the peripheral T cell receptor beta chain repertoire of healthy macaques. Hum Immunol doi
  19. (1991). Cytomegalovirus infection in Gambian mothers and their babies. doi
  20. (1992). De Cock KM: Immunological comparison of HIV-1-, HIV-2- and dually-reactive women delivering in Abidjan, Cote d’Ivoire. Aids doi
  21. (2007). Effector T lymphocytes in well-nourished and malnourished infected children. Clin Exp Immunol doi
  22. (2002). Estimating the precursor frequency of naive antigen-specific CD8 T cells.
  23. (2000). F: Increased cell division but not thymic dysfunction rapidly affects the T-cell receptor excision circle content of the naive T cell population in HIV-1 infection. Nat Med
  24. (1998). HE: Intrathymic non-lymphatic hematopoiesis during mammalian ontogenesis. In Vivo
  25. (2004). Improved thymic function in exclusively breastfed infants is associated with higher interleukin 7 concentrations in their mothers’ breast milk.
  26. (1990). K: Immunodeficiency in HIV-2 infection: a community study from Guinea-Bissau. Aids doi
  27. (1986). Keymer AE: Epidemiology of Heligmosomoides polygyrus in mice: experiments on natural transmission. Parasitology doi
  28. (1998). Koup RA: Changes in thymic function with age and during the treatment of HIV infection.
  29. (2000). Lineage-specific telomere shortening and unaltered capacity for telomerase expression in human T and B lymphocytes with age. doi
  30. (2002). Lisse I: Thymus size at birth is associated with infant mortality: a community study from Guinea-Bissau. Acta Paediatr doi
  31. (2000). LJ: Identification of a human recent thymic emigrant phenotype. doi
  32. (1990). LP: Labelling of T cell subsets under field conditions in tropical countries. Adaptation of the immuno-alkaline phosphatase staining method for blood smears. doi
  33. (1997). Lymphocyte activation and subset redistribution in the peripheral blood in acute malaria illness: distinct gammadelta+ T cell patterns in Plasmodium falciparum and P. vivax infections. Clin Exp Immunol doi
  34. (2000). Maini MK: Differences in the regulation of CD4 and CD8 Tcell clones during immune responses. doi
  35. (1995). Malaria vaccine in children under 12 months of age. Lancet doi
  36. (1990). Malnutrition-induced impairment of resistance against experimental pulmonary tuberculosis. Prog Clin Biol Res
  37. (1997). MK: Effect of zinc supplementation on cell-mediated immunity and lymphocyte subsets in preschool children. Indian Pediatr
  38. (2004). Montesano R: The Gambia Liver Cancer Study: Infection with hepatitis B and C and the risk of hepatocellular carcinoma in West Africa. Hepatology doi
  39. (1997). N’Gom PT, Whittle H: Evaluation of T cell subsets by an immunocytochemical method compared to flow cytometry in four countries. doi
  40. (1999). Neuroendocrine regulation and actions of leptin. Front Neuroendocrinol doi
  41. (2002). Perelson AS: Dynamics of T cells and TCR excision circles differ after treatment of acute and chronic HIV infection. doi
  42. (1993). PK: Clonal predominance of T cell receptors within the CD8+ CD45RO+ subset in normal human subjects.
  43. (1997). Prentice AM: Season of birth predicts mortality in rural Gambia. Nature
  44. (1982). Rahmy AI: A postmortem study of the thymolymphatic system in protein energy malnutrition. J Trop Med Hyg
  45. (2004). RE: Zinc for severe pneumonia in very young children: doubleblind placebo-controlled trial. Lancet doi
  46. (2009). Remoue F: Impact of child malnutrition on the specific anti-Plasmodium falciparum antibody response. doi
  47. (1984). RG: Breast-milk antimicrobial factors of rural Gambian mothers. II. Influence of season and prevalence of infection. Acta Paediatr Scand doi
  48. (1999). RG: Less diarrhoea but no change in growth: 15 years’ data from three Gambian villages. Arch Dis Child doi
  49. (2002). Selenite inhibition of Coxsackie virus B5 replication: implications on the etiology of Keshan disease. doi
  50. (2000). Sleasman JW: TCell receptor Vbeta repertoire CDR3 length diversity differs within CD45RA and CD45RO T-cell subsets in healthy and human immunodeficiency virus-infected children. Clin Diagn Lab Immunol doi
  51. (1999). SR: Leptin protects mice from starvation-induced lymphoid atrophy and increases thymic cellularity in ob/ob mice. doi
  52. (1995). T-cell repertoires in healthy and diseased human tissues analysed by T-cell receptor beta-chain CDR3 size determination: evidence for oligoclonal expansions in tumours and inflammatory diseases. Res Immunol doi
  53. (2007). Tang XY: Analysis of the CDR3 length repertoire and the diversity of TCR alpha chain in human peripheral blood T lymphocytes. Cell Mol Immunol
  54. (2000). Targett GA: Estimates of the infectious reservoir of Plasmodium falciparum malaria in The Gambia and in Tanzania. Trans R Soc Trop Med Hyg doi
  55. (2008). Telomere and adaptive immunity. Mech Ageing Dev doi
  56. (2002). Telomere measurement by quantitative PCR. doi
  57. (1998). The central role of CD4(+) T cells in the antitumor immune response. doi
  58. (1986). The Gambia and Bangladesh: the seasons and diarrhoea. Dialogue Diarrhoea
  59. (1992). The Gambia Hepatitis Intervention Study: follow-up of a cohort of children vaccinated against hepatitis B. J Infect Dis doi
  60. (2002). Thymic size and muscle mass of HIV-infected asymptomatic children from Burkina Faso. J Acquir Immune Defic Syndr doi
  61. (2002). Toubert A: A broad T-cell repertoire Ngom et al.
  62. (1998). Toubert A: The umbilical cord blood alphabeta T-cell repertoire: characteristics of a polyclonal and naive but completely formed repertoire. Blood doi
  63. (1996). Umetsu DT: Cross-linking of the CD40 ligand 1 on human CD4+ T lymphocytes generates a costimulatory signal that up-regulates IL-4 synthesis.
  64. (2008). Verinaud L: Thymic alterations in Plasmodium berghei-infected mice. Cell Immunol doi
  65. (1975). WH: Immune mechanisms in leukemia: suppression of cellular immunity by starvation.
  66. (2007). Whittle HC: Long-term protection against HBV chronic carriage of Gambian adolescents vaccinated in infancy and immune response in HBV booster trial in adolescence. PLoS One doi

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