title: H2-D(d)-mediated upregulation of interleukin-4 production by natural killer T-cell and dendritic cell interaction.
abstract: Natural killer T (NKT) cells are capable of subserving apparently opposite functions, the interferon-gamma (IFN-gamma)-mediated enhancement of host defence and interleukin-4 (IL-4) -mediated immune regulation. Although dendritic cells (DCs) potently activate NKT cells, DC regulation of the IL-4-IFN-gamma balance via NKT-cell activation is not well characterized. In the present study, we examined the effect of DC treatment with CpG oligodeoxynucleotide (ODN), a Toll-like receptor 9 ligand, on the induction of NKT-cell cytokine production. CpG-ODN-conditioned and alpha-galactosylceramide (alpha-GalCer)-loaded myeloid DCs (CpG-DCs) from BALB/c mice showed enhanced ability to induce NKT-cell production of IL-4, but not IFN-gamma, compared to alpha-GalCer-loaded control DCs (not treated with CpG-ODN). The CpG-DCs expressed significantly higher levels of H2-D(d) than control DCs, and blocking of the H2-D(d) and Ly49 receptor interaction during antigen presentation completely abolished the enhanced ability of the CpG-DCs to induce NKT-cell production of IL-4. These findings demonstrate that DC recognition of the CpG motif leads to induction of enhanced IL-4 production by NKT cells via interaction of the augmented H2-D(d) with Ly49 receptors on NKT cells.
authors.affiliation: Division of Immunobiology, Research Section of Pathophysiology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Kazuomi
authors.initials: K
authors.lastname: Mizuuchi
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yanagawa
authors.forename: Kazuya
authors.initials: K
authors.lastname: Iwabuchi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Namba
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Kitaichi
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Ohno
authors.forename: Kazunori
authors.initials: K
authors.lastname: Onoé
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000950:Antigens, Ly / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005699:Galactosylceramides / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology*; D015847:Interleukin-4 / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D055630:Receptors, NK Cell Lectin-Like; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000950:Antigens, Ly; C408982:CPG-oligonucleotide; D005699:Galactosylceramides; D006183:H-2 Antigens; D037181:Lectins, C-Type; D009838:Oligodeoxyribonucleotides; D055630:Receptors, NK Cell Lectin-Like; C493154:alpha-galactosylceramide; D015847:Interleukin-4