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CpG-A oligonucleotides induce a monocyte-derived dendritic cell-like phenotype that preferentially activates CD8 T cells.
CpG-A oligonucleotides induce a monocyte-derived dendritic cell-like phenotype that preferentially activates CD8 T cells.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2003 Apr 01; Vol. 170 (7), pp. 3468-77. - Publication Year :
- 2003
-
Abstract
- 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.
- Subjects :
- CD8-Positive T-Lymphocytes cytology
CD8-Positive T-Lymphocytes metabolism
CD8-Positive T-Lymphocytes virology
Cell Differentiation immunology
Cells, Cultured
Culture Media, Conditioned
Dendritic Cells cytology
Dendritic Cells metabolism
Granulocyte-Macrophage Colony-Stimulating Factor pharmacology
Humans
Immunologic Memory
Immunophenotyping
Influenza A virus immunology
Interferon Type I physiology
Interferon-gamma biosynthesis
Interleukin-15 biosynthesis
Interleukin-4 pharmacology
Leukocyte Common Antigens biosynthesis
Lymphocyte Activation drug effects
Monocytes cytology
Monocytes metabolism
Oligodeoxyribonucleotides immunology
Peptide Fragments immunology
Receptors, CCR7
Receptors, Chemokine biosynthesis
T-Lymphocyte Subsets cytology
T-Lymphocyte Subsets immunology
T-Lymphocyte Subsets metabolism
T-Lymphocyte Subsets virology
Viral Matrix Proteins immunology
Adjuvants, Immunologic pharmacology
CD8-Positive T-Lymphocytes immunology
CpG Islands immunology
Dendritic Cells immunology
Lymphocyte Activation immunology
Monocytes immunology
Oligodeoxyribonucleotides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 170
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 12646607
- Full Text :
- https://doi.org/10.4049/jimmunol.170.7.3468