Skip to main content
Article thumbnail
Location of Repository

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

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, 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: oai:dspace.lib.cranfield.ac.uk:1826/6448
Provided by: Cranfield CERES
Journal:

Suggested articles

Citations

  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

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.