title: CpG ODN enhance antigen-specific NKT cell activation via plasmacytoid dendritic cells.
abstract: Human Valpha24+ Vbeta11+ natural killer T cells (NKT cells) are "natural memory" T cells that detect glycolipid antigens such as alpha-galactosylceramide (alpha-GalCer) presented on CD1d. In the present study we found that highly purified Valpha24+ NKT cells lack TLR9 mRNA, and thus are not sensitive towards stimulation with CpG oligodeoxynucleotides (ODN). Within PBMC, however, CpG ODN synergistically activated NKT cells stimulated with their cognate antigen alpha-GalCer. Depletion of plasmacytoid dendritic cells (PDC) or myeloid dendritic cells (MDC) revealed that both DC subsets were necessary for the synergistic activation of NKT cells by alpha-GalCer and CpG ODN. While PDC were responsible for the stimulation of NKT cells with CpG ODN, MDC but not PDC presented alpha-GalCer via CD1d. Partial activation of NKT cells was mediated by PDC-derived IFN-alpha, whereas full activation of NKT cells as indicated by IFN-gamma production required cell-to-cell contact of PDC and NKT cells in addition to IFN-alpha; OX40 was involved in this interaction. We conclude that CpG-activated PDC enhance alpha-GalCer-specific NKT cell activation, and bias activated NKT cells towards a Th1 phenotype. Our results lead to a novel concept of PDC function: to regulate effector activity of antigen-stimulated T cells in a cell contact-dependent manner without the need of simultaneous presentation of the cognate T cell antigen.
authors: Department of Internal Medicine, Division of Clinical Pharmacology, University of Munich, Munich, Germany.
authors: Anja
authors: A
authors: Marschner
authors: Simon
authors: S
authors: Rothenfusser
authors: Veit
authors: V
authors: Hornung
authors: Domenik
authors: D
authors: Prell
authors: Anne
authors: A
authors: Krug
authors: Miren
authors: M
authors: Kerkmann
authors: Daniela
authors: D
authors: Wellisch
authors: Hendrik
authors: H
authors: Poeck
authors: Andreas
authors: A
authors: Greinacher
authors: Thomas
authors: T
authors: Giese
authors: Stefan
authors: S
authors: Endres
authors: Gunther
authors: G
authors: Hartmann
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D002478:Cells, Cultured; D018899:CpG Islands / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D018984:Epitopes, T-Lymphocyte; D016898:Interferon-alpha; D009838:Oligodeoxyribonucleotides; D007371:Interferon-gamma