Ex Vivo Expanded Human Non-Cytotoxic CD8⁺CD45RC^low/- Tregs Efficiently Delay Skin Graft Rejection and GVHD in Humanized Mice.

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⁺CD45RC^low/- Tregs expressing Foxp3 and producing IFNγ, IL-10, IL-34, and TGFβ to mediate their suppressive activity. We demonstrate that total CD8⁺CD45RC^low/- 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 sign

SUBMITTER: Bezie S 

PROVIDER: S-EPMC5797797 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature