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- Title
Ex Vivo Expanded Human Non-Cytotoxic CD8<sup>+</sup>CD45RC<sup>low/-</sup> Tregs Efficiently Delay Skin Graft Rejection and GVHD in Humanized Mice.
- Authors
Bézie, Séverine; Meistermann, Dimitri; Boucault, Laetitia; Kilens, Stéphanie; Zoppi, Johanna; Autrusseau, Elodie; Donnart, Audrey; Nerrière-Daguin, Véronique; Bellier-Waast, Frédérique; Charpentier, Eric; Duteille, Franck; David, Laurent; Anegon, Ignacio; Guillonneau, Carole
- Abstract
Both CD4c+ and CD8c+ Tregs play a critical role in the control of immune responses and immune tolerance; however, our understanding of CD8c+ Tregs is limited while they are particularly promising for therapeutic application. We report here existence of highly suppressive human CD8c+CD45RClow/- Tregs expressing Foxp3 and producing IFNγ, IL-10, IL-34, and TGFβ to mediate their suppressive activity. We demonstrate that total CD8c+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 CD8c+ Tregs displayed a specific gene signature, upregulated cytokines and expansion in the presence of rapamycin greatly improved proliferation and suppression. We show that CD8c+CD45RClow/- Tregs are equivalent to canonical CD4c+CD25highCD127low/- Tregs for suppression of allogeneic immune responses in vitro. Altogether, our results open new perspectives to tolerogenic strategies in human solid organ transplantation and GVHD.
- Subjects
SKIN grafting; GRAFT rejection; GRAFT versus host disease; IMMUNOREGULATION; IMMUNOLOGICAL tolerance
- Publication
Frontiers in Immunology, 2018, p1
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2017.02014