title: Eminent role of ICOS costimulation for T cells interacting with plasmacytoid dendritic cells.
abstract: CD4+ CD45RO+ T cells could mature freshly isolated human plasmacytoid dendritic cells (PDC) in a superantigen-driven culture in a similar way to recombinant interleukin-3 (IL-3). Mature PDC expressed significantly higher levels of inducible costimulator ligand (ICOS-L), but similar levels of CD80 and CD86, when compared to mature monocyte-derived DC (moDC). We therefore directly compared the capacities of mature PDC and moDC to activate T cells. A similar T helper type 1 (Th1)/Th2 pattern of cytokines was generated in both systems, but significantly higher levels of IL-3, IL-4 and IL-10 were induced by PDC. In T cells interacting with PDC, the ICOS/ICOS-L costimulatory pathway played a pre-eminent role in the generation of IL-3 and IL-10, CD28 was central to the induction of IL-2, and both pathways were equally important for the generation of other cytokines. In cocultures with moDC, the CD28 pathway was dominant over ICOS under all circumstances, except for the ICOS-mediated release of IL-10. In general, our data demonstrate an eminent role of ICOS in the interaction of T cells with PDC, and thus modify the current paradigm of CD28 dominance for the costimulation of T cells interacting with professional antigen-presenting cells. In particular, our data highlight the role of ICOS in the generation of IL-3, a factor central to the biology of human PDC.
authors.affiliation: Molecular Immunology, Robert Koch-Institute, Berlin, Germany.
authors.forename: Marko
authors.initials: M
authors.lastname: Janke
authors.forename: Esther J
authors.initials: EJ
authors.lastname: Witsch
authors.forename: Hans W
authors.initials: HW
authors.lastname: Mages
authors.forename: Andreas
authors.initials: A
authors.lastname: Hutloff
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kroczek
mesh_terms: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D016753:Interleukin-10 / Q000096:biosynthesis; D007377:Interleukin-3 / Q000096:biosynthesis / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation / Q000276:immunology; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D011506:Proteins / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D016207:Cytokines; C556692:ICOS protein, human; C498514:ICOSLG protein, human; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D007377:Interleukin-3; D011506:Proteins; D016753:Interleukin-10; D023201:CD40 Ligand; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1