Ex Vivo Expanded Human Non-Cytotoxic CD8+CD45RClow/-Tregs Efficiently Delay Skin Graft Rejection and GVHD in Humanized Mice - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Frontiers in Immunology Année : 2018

Ex Vivo Expanded Human Non-Cytotoxic CD8+CD45RClow/-Tregs Efficiently Delay Skin Graft Rejection and GVHD in Humanized Mice

Frédérique Bellier-Waast
  • Fonction : Auteur

Résumé

Both CD4+and CD8+Tregs play a critical role in the control of immune responses and immune tolerance; however, our understanding of CD8+Tregs is limited while they are particularly promising for therapeutic application. We report here existence of highly suppressive human CD8+CD45RClow/-Tregs expressing Foxp3 and producing IFNγ, IL-10, IL-34, and TGFβ to mediate their suppressive activity. We demonstrate that total CD8+CD45RClow/-Tregs can be efficiently expanded in the presence of anti-CD3/28 mAbs, high-dose IL-2 and IL-15 and that such expanded Tregs efficiently delay GVHD and human skin transplantation rejection in immune humanized mice. Robustly expanded CD8+Tregs displayed a specific gene signature, upregulated cytokines and expansion in the presence of rapamycin greatly improved proliferation and suppression. We show that CD8+CD45RClow/-Tregs are equivalent to canonical CD4+CD25highCD127low/-Tregs for suppression of allogeneic immune responsesin vitro. Altogether, our results open new perspectives to tolerogenic strategies in human solid organ transplantation and GVHD.
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Dates et versions

hal-01833110 , version 1 (11-07-2018)

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Séverine Bézie, Dimitri Meistermann, Laetitia Boucault, Stéphanie Kilens, Johanna Zoppi, et al.. Ex Vivo Expanded Human Non-Cytotoxic CD8+CD45RClow/-Tregs Efficiently Delay Skin Graft Rejection and GVHD in Humanized Mice. Frontiers in Immunology, 2018, 8, pp.2014. ⟨10.3389/fimmu.2017.02014⟩. ⟨hal-01833110⟩
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