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 responses in vitro. Altogether, our results open new perspectives to tolerogenic strategies in human solid organ transplantation and GVHD.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Bézie S,Meistermann D,Boucault L,Kilens S,Zoppi J,Autrusseau E,Donnart A,Nerrière-Daguin V,Bellier-Waast F,Charpentier E,Duteille F,David L,Anegon I,Guillonneau Cdoi
10.3389/fimmu.2017.02014subject
Has Abstractpub_date
2018-01-31 00:00:00pages
2014issn
1664-3224journal_volume
8pub_type
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journal_title:Frontiers in immunology
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pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
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journal_title:Frontiers in immunology
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