Oligodeoxynucleotides containing CpG motifs induce IL-12, IL-18 and IFN-gamma production in cells from allergic individuals and inhibit IgE synthesis in vitro.
The effects of phosphorothioate oligonucleotides containing CpG motifs (CpG-ODN) on cultured cells from allergic patients and non-atopic individuals were investigated. In peripheral blood mononuclear cells (PBMC) CpG-ODN led to a significant increase of IFN-gamma. By intracellular cytokine staining, IFN-gamma production could be attributed to NK cells and inhibition experiments indicated an IL-12-dependent mechanism. Moreover, CpG-ODN increased mRNA expression of IL-12 and IL-18 in PBMC. In this respect, no significant difference between allergic and non-atopic individuals was observed. Monocyte-derived dendritic cells were identified as one IL-12- and IL-18-producing source. In addition, stimulation of PBMC derived from atopic patients with CpG-ODN led to a considerable increase of polyclonal IgG and IgM synthesis. In contrast, the production of total IgE was suppressed. CpG-ODN induced a significant rise of IgG and IgM specific for allergens to which the patients were sensitized, whereas allergen-specific IgE levels remained unchanged. Our data suggest that CpG-ODN display a strong influence on the ongoing immune response and might represent potential adjuvants for specific immunotherapy of type I allergy.
Bohle
B
B
Department of General and Experimental Pathology, University of Vienna, Austria.
Jahn-Schmid
B
B
Maurer
D
D
Kraft
D
D
Ebner
C
C
D001483:Base Sequence; D018899:CpG Islands; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics; D020382:Interleukin-18 / Q000096:biosynthesis* / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000235:genetics* / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D006255:Rhinitis, Allergic, Seasonal / Q000235:genetics / Q000276:immunology*; D013873:Thionucleotides / Q000235:genetics / Q000494:pharmacology
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D020382:Interleukin-18; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D013873:Thionucleotides; D018664:Interleukin-12; D007073:Immunoglobulin E; D007371:Interferon-gamma