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An orthologous non-MHC locus in rats and mice is linked to CD4+ and CD8+ T-cell proportion

Genes & Immunity volume 18, pages 118–126 (2017)Cite this article

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Abstract

CD4+ and CD8+ T cells have a central role in the immune system due to their ability to protect against infection and cancer development without targeting self. Consequently, changes in CD4+ and CD8+ T-cell homeostasis can be indicative of an array of serious illnesses, ranging from viral infections to autoimmune diseases. In addition to environmental influences, there is evidence for a genetic component regulating the proportion of CD4+ and CD8+ T cells in lymphoid organs. Indeed, identifying the genetic determinants defining the frequency of the T-cell subsets is critical as it may reveal a targetable genetic pathway to modulate CD4+ and CD8+ T-cell numbers, which could be of clinical relevance for multiple disease settings. In this study, we aim to uncover non-MHC genetic factors regulating the proportion of CD4+ and CD8+ T cells in lymphoid tissues. By investigating linkage analyses on three independent F2 cohorts, namely a rat F2 (BBDP × ACI.1U.LYP) cohort, a mouse 3A9 TCR transgenic F2 (B10.BR × NOD.H2k) cohort and a mouse F2 (C57BL/6 × FVB/N) cohort, we uncover an orthologous non-MHC locus on rat chromosome 1 and mouse chromosome 7 that is linked to T-cell proportion amongst total lymphocytes.

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Acknowledgements

This work was supported by a grant from the Canadian Diabetes Association (OG-3-13-4018) to SL. SL holds a Senior scholarship and RC holds studentship from Fonds de recherche du Québec – Santé.

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Author notes

  1. D Franckaert and R Collin: These authors contributed equally to this work.

Authors and Affiliations

  1. VIB Center for Brain & Disease Research, Leuven, Belgium

    D Franckaert, J Dooley & A Liston

  2. Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium

    D Franckaert, J Dooley & A Liston

  3. Division of Immunology-oncology, Maisonneuve-Rosemont Hospital, Research Center, Montréal, QC, Canada

    R Collin, E E Hillhouse & S Lesage

  4. Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC, Canada

    R Collin, E E Hillhouse & S Lesage

  5. Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada

    R H Wallis & P Poussier

  6. Biological Sciences Platform, Sunnybrook Research Institute, Toronto, ON, Canada

    R H Wallis & P Poussier

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  1. D Franckaert
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Correspondence to E E Hillhouse or S Lesage.

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Franckaert, D., Collin, R., Dooley, J. et al. An orthologous non-MHC locus in rats and mice is linked to CD4+ and CD8+ T-cell proportion. Genes Immun 18, 118–126 (2017). https://doi.org/10.1038/gene.2017.9

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