Title |
Ex Vivo Expanded Human Non-Cytotoxic CD8+CD45RClow/− Tregs Efficiently Delay Skin Graft Rejection and GVHD in Humanized Mice
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Published in |
Frontiers in immunology, January 2018
|
DOI | 10.3389/fimmu.2017.02014 |
Pubmed ID | |
Authors |
Séverine Bézie, Dimitri Meistermann, Laetitia Boucault, Stéphanie Kilens, Johanna Zoppi, Elodie Autrusseau, Audrey Donnart, Véronique Nerrière-Daguin, Frédérique Bellier-Waast, Eric Charpentier, Franck Duteille, Laurent David, Ignacio Anegon, Carole Guillonneau |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 1 | 50% |
Unknown | 1 | 50% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 50 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 10 | 20% |
Student > Ph. D. Student | 7 | 14% |
Student > Doctoral Student | 6 | 12% |
Other | 4 | 8% |
Student > Master | 4 | 8% |
Other | 6 | 12% |
Unknown | 13 | 26% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 11 | 22% |
Immunology and Microbiology | 10 | 20% |
Agricultural and Biological Sciences | 5 | 10% |
Biochemistry, Genetics and Molecular Biology | 4 | 8% |
Computer Science | 1 | 2% |
Other | 5 | 10% |
Unknown | 14 | 28% |