Immunotherapeutic uses of CpG oligodeoxynucleotides View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2004-04

AUTHORS

Dennis M. Klinman

ABSTRACT

Key PointsSingle-stranded DNA containing CpG motifs triggers an innate immune response that is characterized by the production of polyreactive immunoglobulin and the production of T helper 1 (TH1)-type and pro-inflammatory cytokines, and chemokines.CpG DNA interacts with Toll-like receptor 9 (TLR9) in the endosomal vesicles of human B cells and plasmacytoid dendritic cells, initiating a signalling cascade that proceeds through myeloid differentiation primary response gene 88 (MYD88) and culminates in the translocation of nuclear factor-κB (NF-κB) from the cytoplasm to the nucleus. The subsequent cytokine response indirectly activates various other cell types, including natural killer cells, T cells and macrophages.Human immune cells are stimulated by three structurally distinct classes of CpG oligodeoxynucleotide (ODN). Different types of immune response are triggered by each class of ODN.The innate immune response that is triggered by CpG ODNs improves host resistance to a wide range of pathogenic bacteria, viruses and parasites.By facilitating the production of TH1-type and pro-inflammatory cytokines, and promoting the functional maturation of professional antigen-presenting cells, CpG ODNs accelerate and boost the generation of antigen-specific immunity when co-administered with vaccines.By promoting TH1-biased immunity, CpG ODNs dampen the development of TH2-cell-mediated allergic responses. Reduced allergen-specific IgE production and improved lung function accompany the administration of CpG ODNs with allergen.CpG DNA has the potential to worsen organ-specific autoimmune disease and cause other pathological changes when administered repeatedly at a high dose. However, the regimens that are required to achieve the therapeutic effects described above have not caused adverse events in normal animals or humans.CpG ODNs have been administered safely to more than 500 individuals. Preclinical and clinical results indicate that these agents will be of therapeutic value in the treatment of allergic disorders and for improving host immunity against infectious pathogens. More... »

PAGES

249-259

Journal

TITLE

Nature Reviews Immunology

ISSUE

4

VOLUME

4

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nri1329

    DOI

    http://dx.doi.org/10.1038/nri1329

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1032165765

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/15057783


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