Analysis of the peripheral T-cell repertoire in kidney transplant patients

Authors

  • Patrick Miqueu,

    1. INSERM Unité 643, CHU de Nantes, Institut de Transplantation et de Recherche en Transplantation, Université de Nantes, Faculté de Médecine de Nantes. RTRS “Centaure”, Nantes, France
    2. TcLand Expression S.A., Nantes, France
    3. EA 4275 Biostatistique, Recherche Clinique & Mesures Subjectives en Santé, Faculté de Pharmacie, Nantes, France
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    • These authors have contributed equally as first and senior authors, respectively.

  • Nicolas Degauque,

    1. INSERM Unité 643, CHU de Nantes, Institut de Transplantation et de Recherche en Transplantation, Université de Nantes, Faculté de Médecine de Nantes. RTRS “Centaure”, Nantes, France
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    • These authors have contributed equally as first and senior authors, respectively.

  • Marina Guillet,

    1. TcLand Expression S.A., Nantes, France
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  • Magali Giral,

    1. INSERM Unité 643, CHU de Nantes, Institut de Transplantation et de Recherche en Transplantation, Université de Nantes, Faculté de Médecine de Nantes. RTRS “Centaure”, Nantes, France
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  • Catherine Ruiz,

    1. TcLand Expression S.A., Nantes, France
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  • Annaïck Pallier,

    1. INSERM Unité 643, CHU de Nantes, Institut de Transplantation et de Recherche en Transplantation, Université de Nantes, Faculté de Médecine de Nantes. RTRS “Centaure”, Nantes, France
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  • Cécile Braudeau,

    1. INSERM Unité 643, CHU de Nantes, Institut de Transplantation et de Recherche en Transplantation, Université de Nantes, Faculté de Médecine de Nantes. RTRS “Centaure”, Nantes, France
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  • Gwenaëlle Roussey-Kesler,

    1. INSERM Unité 643, CHU de Nantes, Institut de Transplantation et de Recherche en Transplantation, Université de Nantes, Faculté de Médecine de Nantes. RTRS “Centaure”, Nantes, France
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  • Joanna Ashton-Chess,

    1. INSERM Unité 643, CHU de Nantes, Institut de Transplantation et de Recherche en Transplantation, Université de Nantes, Faculté de Médecine de Nantes. RTRS “Centaure”, Nantes, France
    2. TcLand Expression S.A., Nantes, France
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  • Jean-Christophe Doré,

    1. UMR 5154, CNRS/MNHN, Paris, France
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  • Eric Thervet,

    1. Université Paris Descartes and Hôpital Necker, AP-HP, Paris, France
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  • Christophe Legendre,

    1. Université Paris Descartes and Hôpital Necker, AP-HP, Paris, France
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  • Maria P. Hernandez-Fuentes,

    1. Medical Research Council Center for Transplantation, King's College London, School of Medicine, Guy's Hospital, London, UK
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  • Anthony N. Warrens,

    1. Immunology and Renal Medicine, Imperial College, London, UK
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  • Michel Goldman,

    1. Institute for Medical Immunology, Université Libre de Bruxelles, Charleroi, Belgium
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  • Hans-Dieter Volk,

    1. Institute for Medical Immunology and Berlin-Brandenburg Center for Regenerative Medicine, Charité University Medicine, Berlin, Germany
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  • Uwe Janssen,

    1. MACSmolecular Business Unit, Miltenyi Biotec GmbH, Cologne, Germany
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  • Kathryn J. Wood,

    1. Transplantation Research Immunology Group, Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, UK
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  • Robert I. Lechler,

    1. Medical Research Council Center for Transplantation, King's College London, School of Medicine, Guy's Hospital, London, UK
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  • Dominique Bertrand,

    1. INRA-BIA, Nantes, France
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  • Véronique Sébille,

    1. EA 4275 Biostatistique, Recherche Clinique & Mesures Subjectives en Santé, Faculté de Pharmacie, Nantes, France
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  • Jean-Paul Soulillou,

    Corresponding author
    1. INSERM Unité 643, CHU de Nantes, Institut de Transplantation et de Recherche en Transplantation, Université de Nantes, Faculté de Médecine de Nantes. RTRS “Centaure”, Nantes, France
    • INSERM U643 30, Bd Jean Monnet, 44093 Nantes Cedex 1, France Fax: +33-2-40-08-74-11
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    • These authors have contributed equally as first and senior authors, respectively.

  • Sophie Brouard

    1. INSERM Unité 643, CHU de Nantes, Institut de Transplantation et de Recherche en Transplantation, Université de Nantes, Faculté de Médecine de Nantes. RTRS “Centaure”, Nantes, France
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    • These authors have contributed equally as first and senior authors, respectively.


Abstract

The long-term stability of renal grafts depends on the absence of chronic rejection. As T cells play a key role in rejection processes, analyzing the T-cell repertoire may be useful for understanding graft function outcomes. We have therefore investigated the power of a new statistical tool, used to analyze the peripheral blood TCR repertoire, for determining immunological differences in a group of 229 stable renal transplant patients undergoing immunosuppression. Despite selecting the patients according to stringent criteria, the patients displayed heterogeneous T-cell repertoire usage, ranging from unbiased to highly selected TCR repertoires; a skewed TCR repertoire correlating with an increase in the CD8+/CD4+ T-cell ratio. T-cell repertoire patterns were compared in patients with clinically opposing outcomes i.e. stable drug-free operationally tolerant recipients and patients with the “suspicious” form of humoral chronic rejection and were found significantly different, from polyclonal to highly selected TCR repertoires, respectively. Moreover, a selected TCR repertoire was found to positively correlate with the Banff score grade. Collectively, these data suggest that TCR repertoire categorization might be included in the calculation of a composite score for the follow-up of patients after kidney transplantation.

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