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Final Program


Final Program

Stem Cell and Organ Transplantation

Human Microbiota-Reactive DP8a Regulatory T Cells Protect Against Transplantation-Related Disorders

Tu201 - Human Microbiota-reactive dp8a Regulatory T Cells Protect Against Transplantation-related Disorders

Tuesday, June 24, 2025
6:00pm - 7:30pm East Coast USA Time
  • MV

    Margaux Verdon

    PhD student
    INSERM U1302 - Immunology and New Concepts in Immunotherapy (INCIT)
    Nantes, Pays de la Loire, France

  • MD

    Margaux De Seilhac

    INSERM UMR 1302 Immunology and New Concepts in ImmunoTherapy (INCIT)

  • PC

    Patrice Chevallier, MD/PhD

    Clinical Hematology Department, Nantes University Hospital

  • FH

    Fabienne Haspot, PhD

    Researcher/PhD
    INSERM UMR 1064 Center for Research in Transplantation and Translational Immunology (CR2TI)
    Nantes, Pays de la Loire, France

  • VD

    Véronique Daguin, PhD

    INSERM UMR 1064 Center for Research in Transplantation and Translational Immunology (CR2TI)
    Nantes, Pays de la Loire, France

  • SL

    Sylvia Lambot

    INSERM UMR 1302 Immunology and New Concepts in ImmunoTherapy (INCIT)

  • CV

    Caroline Vignes, PhD

    INSERM UMR 1302 Immunology and New Concepts in ImmunoTherapy (INCIT)

  • VL

    Valentin Letailleur, MD

    Clinical Hematology Department, Nantes University Hospital

  • TG

    Thierry Guillaume, MD/PhD

    Clinical Hematology Department, Nantes University Hospital

  • PP

    Pierre Peterlin, MD

    Clinical Hematology, Nantes University Hospital

  • AG

    Alice Garnier, MD

    Clinical Hematology Department, Nantes University Hospital

  • AL

    Amandine Le Bourgeois, MD

    Clinical Hematology Department, Nantes University Hospital

  • MG

    Magali Giral, PhD

    PU-PH
    INSERM UMR 1064 Center for Research in Transplantation and Translational Immunology (CR2TI)
    Nantes, Pays de la Loire, France

  • SB

    Sophie Brouard, PhD

    DR1 - Team leader
    Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France
    Nantes, Pays de la Loire, France

  • CM

    Christophe Masset, MD

    INSERM UMR 1064 Center for Research in Transplantation and Translational Immunology (CR2TI)

  • DD

    Didier Ducloux, MD

    Franche-Comté University, Besançon University Hospital, Etablissement Français du Sang Bourgogne Franche-Comté, INSERM, Unité Mixte de Recherche 1098, RIGHT Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon, France.

  • EG

    Emilie Gaiffe, PhD

    Franche-Comté University, Besançon University Hospital, Etablissement Français du Sang Bourgogne Franche-Comté, INSERM, Unité Mixte de Recherche 1098, RIGHT Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon, France.

  • MJ

    Maxime Jullien, MD

    Clinical Hematology Department, Nantes University Hospital

  • FA

    Fréderic Altare, PhD

    INSERM UMR 1302 Immunology and New Concepts in ImmunoTherapy (INCIT)

  • FJ

    Francine Jotereau, Pr

    INSERM UMR 1302 Immunology and New Concepts in ImmunoTherapy (INCIT)

  • EG

    Emmanuelle Godefroy, PhD

    INSERM UMR 1302 Immunology and New Concepts in ImmunoTherapy (INCIT)

Abstract Text: Alteration of intestinal microbiota, called dysbiosis, is associated with numerous pathologies, including complications following allogeneic transplantations like acute graft-versus-host disease (aGvHD) and kidney transplant rejection. These conditions, have been associated with a low abundance of the commensal Faecalibacterium duncaniae (F. duncaniae) in patients’ stools. Interestingly, our team has identified a Treg subset, called DP8a, reactive to F. duncaniae and whose suppressive function rely on the CD39- and CD73-dependent purinergic pathway, which had also been implicated in these two disorders.
Using two cohorts (507 and 230) kidney-transplanted patients (DIVAT and ORLY-Est, respectively), we observed that CD73+ DP8a Tregs were significantly increased post-transplantation in patients who will not reject their graft, as compared to patients who will reject it later on, making those cells both a potential predictive biomarker and a therapeutic tool. This increase was not observed pre-transplantation, indicating that DP8a Treg activation occurred upon transplantation. In another transplantation context, using a cohort of 62 patients treated by allogeneic stem cell transplantation, we observed specific alterations of the DP8a Treg subset in patients who developed aGvHD. Remarkably, not only donor-derived CD73+ DP8a Tregs were decreased, but also displayed lower host-reactivities in aGvHD patients, as compared to aGvHD-free patients. Cloning alloreactive DP8a T cells demonstrated that they could cross-react with F. duncaniae antigens and harbored potent regulatory functions.
Altogether, these results strongly support that the DP8a Treg subset could play a key role in tolerance to allogeneic transplantation, possibly through their cross-reaction(s) with alloantigens, hence providing anti-inflammatory protection against these transplantation disorders.