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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Autoimmune Diseases / immunology*
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CD3 Complex / immunology
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CD4-Positive T-Lymphocytes / immunology*
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Dendritic Cells / immunology*
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Female
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Forkhead Transcription Factors / immunology*
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Graft vs Host Disease / immunology
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Immune Tolerance / immunology*
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Interleukin-10 / immunology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Inbred DBA
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Protein Serine-Threonine Kinases / immunology
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Receptor, Transforming Growth Factor-beta Type II
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Receptors, Transforming Growth Factor beta / immunology
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Signal Transduction / immunology
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T-Lymphocytes, Regulatory / immunology*
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Transforming Growth Factor beta / immunology*
Substances
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CD3 Complex
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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Receptors, Transforming Growth Factor beta
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Transforming Growth Factor beta
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Interleukin-10
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Protein Serine-Threonine Kinases
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Receptor, Transforming Growth Factor-beta Type II