Description:
<jats:title>Abstract</jats:title><jats:p>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<jats:sup>+</jats:sup> and CD8<jats:sup>+</jats:sup> 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 <jats:italic>via</jats:italic> B7‐H1 and sialoadhesin is crucial for the induction of human IL‐35<jats:sup>+</jats:sup> Treg. These results demonstrate a novel pathway and its components for the induction of immune‐inhibitory T cells.</jats:p>