CpG-A oligonucleotides induce a monocyte-derived dendritic cell-like phenotype that preferentially activates CD8 T cells

Détails

ID Serval
serval:BIB_FC3321B173EF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
CpG-A oligonucleotides induce a monocyte-derived dendritic cell-like phenotype that preferentially activates CD8 T cells
Périodique
Journal of Immunology
Auteur(s)
Krug  A., Rothenfusser  S., Selinger  S., Bock  C., Kerkmann  M., Battiany  J., Sarris  A., Giese  T., Speiser  D., Endres  S., Hartmann  G.
ISSN
0022-1767 (Print)
Statut éditorial
Publié
Date de publication
04/2003
Volume
170
Numéro
7
Pages
3468-77
Notes
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Apr 1
Résumé
Human B cells and plasmacytoid dendritic cells recognize CpG motifs within microbial DNA via Toll-like receptor 9. Two functionally distinct types of CpG motif containing oligonucleotides (CpG ODN) have been described, CpG-A and CpG-B. In contrast to CpG-B, CpG-A induces high amounts of type I IFN (IFN-alpha and IFN-beta) in plasmacytoid dendritic cells. In the present study, we examined the effects of CpG-A on human primary monocytes. In PBMC stimulated with CpG-A and GM-CSF, monocytes showed excellent survival, increased in size and granularity, and within 3 days developed a dendritic cell-like phenotype that was characterized by down-regulation of CD14, partial up-regulation of CCR7, and an increased surface expression of costimulatory and Ag-presenting molecules. This effect could be inhibited by a combination of blocking Abs to type I IFN, and no such CpG-A-induced changes were observed in purified monocytes. Although IL-12 production by this dendritic cell-like phenotype required additional stimulation with CD40 ligand, this cell type spontaneously up-regulated IL-15 expression. Consistent with the known effect of IL-15 on effector and memory CD8 T cells, the frequency of CCR7(-)/CD45RA(-) CD8 T cells was selectively increased in allogeneic T cell assays. Furthermore, this dendritic cell type was more potent to support both the generation and the IFN-gamma production of autologous influenza matrix peptide-specific memory CD8 T cells as compared with dendritic cells generated in the presence of GM-CSF and IL-4. In conclusion, monocytes exposed to the cytokine milieu provided by CpG-A rapidly develop a dendritic cell-like phenotype that is well equipped to support CD8 T cell responses.
Mots-clé
Adjuvants, Immunologic/*pharmacology Antigens, CD45/biosynthesis CD8-Positive T-Lymphocytes/cytology/*immunology/metabolism/virology Cell Differentiation/immunology Cells, Cultured CpG Islands/*immunology Culture Media, Conditioned Dendritic Cells/cytology/*immunology/metabolism Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology Humans Immunologic Memory Immunophenotyping Influenza A virus/immunology Interferon Type I/physiology Interferon Type II/biosynthesis Interleukin-15/biosynthesis Interleukin-4/pharmacology Lymphocyte Activation/drug effects/*immunology Monocytes/cytology/*immunology/metabolism Oligodeoxyribonucleotides/immunology/*pharmacology Peptide Fragments/immunology Receptors, Chemokine/biosynthesis T-Lymphocyte Subsets/cytology/immunology/metabolism/virology Viral Matrix Proteins/immunology
Pubmed
Web of science
Création de la notice
28/01/2008 12:33
Dernière modification de la notice
20/08/2019 17:27
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