IL-10/IFNγ co-expressing CD4(+) T cells induced by IL-10 DC display a regulatory gene profile and downmodulate T cell responses.

Induced regulatory T cells (iTreg) are imperative for tolerance induction and spreading of infectious tolerance. Ex vivo generated tolerogenic dendritic cells (tDCs) have strong therapeutic potential to induce antigen-specific iTreg. We previously demonstrated that IL-10 tDC-primed T cells are very suppressive and produce IL-10. Here, we show that the majority of IL-10(+) T cells co-express IFNγ, giving rise to the question whether these cells are proinflammatory or regulatory. Whole genome gene expression analysis revealed a strong regulatory gene profile and a suppressed Th1 gene profile for IL-10/IFNγ co-expressing CD4(+) T cells. Protein analysis confirmed an extensive regulatory phenotype for IL-10(+)/IFNγ(+) T cells, with specific enhanced expression of GARP and PD-1. In line with these data, isolated IL-10(+)/IFNγ(+) T cells displayed potent suppressive capacity. Thus, IL-10/IFNγ co-expressing CD4(+) T cells induced by IL-10 tDC show dominance of immunomodulation over Th1-mediated immunoactivation and can contribute to induction or spreading of immunological tolerance.