Abstract
IL-35 is a heterodimer of EBV-induced gene 3 and of the p35 subunit of IL-12, and recently identified as an inhibitory cytokine produced by natural Treg in mice, but not in humans. Here we demonstrate that DC activated by human rhinoviruses (R-DC) induce IL-35 production and release, as well as a suppressor function in CD4(+) and CD8(+) T cells derived from human peripheral blood but not in naïve T cells from cord blood. The induction of IL-35-producing T cells by R-DC was FOXP3-independent, but blocking of B7-H1 (CD274) and sialoadhesin (CD169) on R-DC with mAb against both receptors prevented the induction of IL-35. Thus, the combinatorial signal delivered by R-DC to T cells via B7-H1 and sialoadhesin is crucial for the induction of human IL-35(+) Treg. These results demonstrate a novel pathway and its components for the induction of immune-inhibitory T cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, CD / metabolism*
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B7-H1 Antigen
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Blotting, Western
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / metabolism
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Cell Line
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Cell Proliferation / drug effects
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Cells, Cultured
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Coculture Techniques
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Culture Media, Conditioned / chemistry
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Culture Media, Conditioned / pharmacology
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Dendritic Cells / cytology
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Dendritic Cells / metabolism*
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Flow Cytometry
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Forkhead Transcription Factors / genetics
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Forkhead Transcription Factors / metabolism
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Host-Pathogen Interactions
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Humans
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Interferon-alpha / metabolism
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Interleukin-10 / metabolism
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Interleukins / genetics
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Interleukins / metabolism*
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Membrane Glycoproteins / metabolism*
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Receptors, Immunologic / metabolism*
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Reverse Transcriptase Polymerase Chain Reaction
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Rhinovirus / physiology*
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Sialic Acid Binding Ig-like Lectin 1
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T-Lymphocytes, Regulatory / cytology
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T-Lymphocytes, Regulatory / metabolism*
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T-Lymphocytes, Regulatory / virology
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Transforming Growth Factor beta / metabolism
Substances
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Antigens, CD
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B7-H1 Antigen
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CD274 protein, human
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Culture Media, Conditioned
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FOXP3 protein, human
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Forkhead Transcription Factors
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Interferon-alpha
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Interleukins
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Membrane Glycoproteins
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Receptors, Immunologic
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SIGLEC1 protein, human
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Sialic Acid Binding Ig-like Lectin 1
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Siglec1 protein, mouse
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Transforming Growth Factor beta
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interleukin-35, human
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Interleukin-10