title: Double stranded RNA- relative to other TLR ligand-activated dendritic cells induce extremely polarized human Th1 responses.
abstract: To better understand the relative efficiencies of using different TLR ligand-activated DCs to induce human CD4(+) T lymphocyte responses, human DCs were activated with two viral and two bacterial TLR ligands, and their production of IL12, TNFalpha, and IL10 was examined. While the two viral TLR ligands (ssRNA and dsRNA) induced DC production of detectable levels of IL12p70, DCs activated by the two bacterial TLR ligands (LPS and flagellin) induced increased proliferation of human allogeneic naïve CD4(+) T cells. dsRNA-activated DCs induced increased Th1 and decreased Th2 differentiation, resulting in extremely polarized responses relative to those induced by unstimulated and other TLR ligand-activated DCs. Neutralization of IL12p70 abrogated most of the Th1 skewing induced by all TLR ligand-activated moDCs. Collectively, these results demonstrate that dsRNA-activated DCs induce more highly polarized human Th1 responses than the other TLR ligand-activated DCs tested here. These results have implications for TLR ligands in immunotherapy.
authors.affiliation: Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, USA.
authors.forename: Risa K
authors.initials: RK
authors.lastname: Benwell
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Hruska
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Fritsche
authors.forename: David R
authors.initials: DR
authors.lastname: Lee
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005408:Flagellin / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D012328:RNA Viruses / Q000276:immunology / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D051193:Toll-Like Receptors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D008024:Ligands; D008070:Lipopolysaccharides; D012330:RNA, Double-Stranded; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D005408:Flagellin; D016753:Interleukin-10; D018664:Interleukin-12