title: IL-10/IFNγ co-expressing CD4(+) T cells induced by IL-10 DC display a regulatory gene profile and downmodulate T cell responses.
abstract: 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.
authors.affiliation: Department of Immunopathology, Sanquin Blood Supply, Division Research and Landsteiner Laboratory, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Martine A
authors.initials: MA
authors.lastname: Boks
authors.affiliation: Department of Immunopathology, Sanquin Blood Supply, Division Research and Landsteiner Laboratory, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Judith R
authors.initials: JR
authors.lastname: Kager-Groenland
authors.affiliation: Department of Immunopathology, Sanquin Blood Supply, Division Research and Landsteiner Laboratory, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: S Marieke
authors.initials: SM
authors.lastname: van Ham
authors.affiliation: Department of Immunopathology, Sanquin Blood Supply, Division Research and Landsteiner Laboratory, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: a.tenbrinke@sanquin.nl.
authors.forename: Anja
authors.initials: A
authors.lastname: ten Brinke
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015536:Down-Regulation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics* / Q000276:immunology*; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: C508609:IL10 protein, human; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: Cytokines; Micro array; Regulatory T cells; Suppression; T helper cell plasticity; Tolerogenic dendritic cells