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Genetic determinism in the relationship between human CD4 + and CD8 + T lymphocyte populations?

Genes & Immunity volume 2, pages 381–387 (2001)Cite this article

Abstract

The adaptive immune system in mammals acts in a coordinated manner to eliminate environmentally derived pathogens. Humans, mice and rats show within species variation in the levels and ratios of their peripheral CD4+ and CD8+ T cells and to a significant degree this variation is under the control of polymorphic genes. Whether genes act separately to specify CD4+ and CD8+ subpopulation levels or whether CD8+ variation is controlled through gene and environmental action on CD4+ cells or vice versa, is not known. We use a quantitative modelling approach in identical and non-identical female human twins to delineate the lines of control which act upon and between CD4+ and CD8+ subsets. The major findings of the study are: (1) genetic variation controls CD8+ T cell levels through two major routes—the first is via an effect on CD4+ T cells which accounts for the observed co-variation between CD4+ and CD8+ T cells, the second is through direct action on CD8+ T cell levels. (2) No evidence of a gene effect from CD8+ T cells on CD4+ cells is observed. Our findings have implications for the evolution of the complex defence system of which CD4+ and CD8+ T cells are a crucial part and encourage further work towards locating common pleiotropic quantitative trait loci responsible for variation in numbers of T cells.

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Acknowledgements

MAH is an Arthritis Research Campaign Postdoctoral Research Fellow. Avrion Mitchison is gratefully acknowledged for his comments on the manuscript.

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Author notes

  1. H Snieder

    Present address: Georgia Prevention Institute, Medical College of Georgia, Augusta, 30912, GA, USA

Authors and Affiliations

  1. Twin Research & Genetic Epidemiology Unit, St. Thomas’ Hospital, London, UK

    KR Ahmadi, H Snieder & TD Spector

  2. Department of Rheumatology, Molecular Immunogenetics Unit, GKT School of Medicine, King’s College, London, UK

    KR Ahmadi, MA Hall & JS Lanchbury

  3. South Thames Tissue Typing, Guy’s Hospital, London, UK

    P Norman & RW Vaughan

Authors
  1. KR Ahmadi
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  2. MA Hall
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  3. P Norman
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  4. RW Vaughan
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  5. H Snieder
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  6. TD Spector
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  7. JS Lanchbury
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Corresponding author

Correspondence to JS Lanchbury.

Additional information

We are grateful to the Special Trustees of St Thomas’ Hospital and Gemini Genomics Limited for support in initiating this research. The Twin Research Unit also receives support from the Arthritis Research Campaign, the Wellcome Trust and the Chronic Disease Research Foundation.

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Ahmadi, K., Hall, M., Norman, P. et al. Genetic determinism in the relationship between human CD4 + and CD8 + T lymphocyte populations?. Genes Immun 2, 381–387 (2001). https://doi.org/10.1038/sj.gene.6363796

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