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  • Title: Polyclonal CD4+Foxp3+ Treg cells induce TGFβ-dependent tolerogenic dendritic cells that suppress the murine lupus-like syndrome.
    Author: Lan Q, Zhou X, Fan H, Chen M, Wang J, Ryffel B, Brand D, Ramalingam R, Kiela PR, Horwitz DA, Liu Z, Zheng SG.
    Journal: J Mol Cell Biol; 2012 Dec; 4(6):409-19. PubMed ID: 22773728.
    Abstract:
    Interplay between Foxp3(+) regulatory T cells (Treg) and dendritic cells (DCs) maintains immunologic tolerance, but the effects of each cell on the other are not well understood. We report that polyclonal CD4(+)Foxp3(+) Treg cells induced ex vivo with transforming growth factor beta (TGFβ) (iTreg) suppress a lupus-like chronic graft-versus-host disease by preventing the expansion of immunogenic DCs and inducing protective DCs that generate additional recipient CD4(+)Foxp3(+) cells. The protective effects of the transferred iTreg cells required both interleukin (IL)-10 and TGFβ, but the tolerogenic effects of the iTreg on DCs, and the immunosuppressive effects of these DCs were exclusively TGFβ-dependent. The iTreg were unable to tolerize Tgfbr2-deficient DCs. These results support the essential role of DCs in 'infectious tolerance' and emphasize the central role of TGFβ in protective iTreg/DC interactions in vivo.
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