Human rhinoviruses induce IL-35-producing Treg via induction of B7-H1 (CD274) and sialoadhesin (CD169) on DC.
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.
Seyerl
Maria
M
Institute of Immunology, Medical University of Vienna, Austria.
Kirchberger
Stefanie
S
Majdic
Otto
O
Seipelt
Joachim
J
Jindra
Christoph
C
Schrauf
Catharina
C
Stöckl
Johannes
J
D015703:Antigens, CD / Q000378:metabolism*; D060890:B7-H1 Antigen; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012229:Rhinovirus / Q000502:physiology*; D063267:Sialic Acid Binding Ig-like Lectin 1; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D016212:Transforming Growth Factor beta / Q000378:metabolism
D015703:Antigens, CD; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D017077:Culture Media, Conditioned; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016898:Interferon-alpha; D007378:Interleukins; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C571166:SIGLEC1 protein, human; D063267:Sialic Acid Binding Ig-like Lectin 1; C571167:Siglec1 protein, mouse; D016212:Transforming Growth Factor beta; C532417:interleukin-35, human; D016753:Interleukin-10