Abstract
Bacterial DNA and immunostimulatory CpG oligodeoxynucleotides (ODNs) activate the innate immune system to produce proinflammatory cytokines. Shown to be potent Th1-like adjuvants, stimulatory CpG motifs are currently used as effective therapeutic vaccines for various animal models of infectious diseases, tumors, allergies, and autoimmune diseases. In this study, we show that the application of an immunomodulatory GpG ODN, with a single base switch from CpG to GpG, can effectively inhibit the activation of Th1 T cells associated with autoimmune disease. Moreover, this immunomodulatory GpG ODN suppresses the severity of experimental autoimmune encephalomyelitis in mice, a prototypic Th1-mediated animal disease model for multiple sclerosis.
Publication types
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, P.H.S.
MeSH terms
- Adjuvants, Immunologic / administration & dosage
- Adjuvants, Immunologic / genetics
- Adjuvants, Immunologic / pharmacology*
- Animals
- Antigen-Presenting Cells / immunology
- Antigen-Presenting Cells / metabolism
- Antigens, CD1 / biosynthesis
- Autoimmune Diseases / immunology*
- Autoimmune Diseases / pathology*
- Cells, Cultured
- Cytokines / antagonists & inhibitors
- Cytokines / biosynthesis
- Dinucleoside Phosphates / administration & dosage
- Dinucleoside Phosphates / immunology
- Dinucleoside Phosphates / pharmacology*
- Down-Regulation / immunology
- Encephalomyelitis, Autoimmune, Experimental / immunology
- Encephalomyelitis, Autoimmune, Experimental / prevention & control
- Female
- GC Rich Sequence / genetics
- GC Rich Sequence / immunology*
- Glycoproteins / biosynthesis
- Growth Inhibitors / pharmacology
- Histocompatibility Antigens Class II / biosynthesis
- I-kappa B Proteins / antagonists & inhibitors
- I-kappa B Proteins / metabolism
- Immunity, Innate / genetics
- Immunosuppressive Agents / administration & dosage
- Immunosuppressive Agents / pharmacology
- Lymphocyte Activation / genetics
- Lymphocyte Activation / immunology
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Mice, Knockout
- Mice, Transgenic
- Myelin Basic Protein / antagonists & inhibitors
- Myelin Basic Protein / biosynthesis
- Myelin Basic Protein / genetics
- Myelin Proteolipid Protein / antagonists & inhibitors
- Myelin Proteolipid Protein / physiology
- NF-KappaB Inhibitor alpha
- NF-kappa B / antagonists & inhibitors
- NF-kappa B / metabolism
- Oligodeoxyribonucleotides / administration & dosage
- Oligodeoxyribonucleotides / immunology
- Oligodeoxyribonucleotides / pharmacology*
- Peptide Fragments / antagonists & inhibitors
- Peptide Fragments / biosynthesis
- Peptide Fragments / genetics
- Peptide Fragments / physiology
- Phosphorylation
- Serine / metabolism
- Spleen / cytology
- Spleen / immunology
- Th1 Cells / immunology
- Th1 Cells / metabolism
- Th2 Cells / immunology
- Up-Regulation / immunology
Substances
- Adjuvants, Immunologic
- Antigens, CD1
- CD1C protein, human
- Cytokines
- Dinucleoside Phosphates
- Glycoproteins
- GpG-oligonucleotide
- Growth Inhibitors
- Histocompatibility Antigens Class II
- I-kappa B Proteins
- Immunosuppressive Agents
- Myelin Basic Protein
- Myelin Proteolipid Protein
- NF-kappa B
- NFKBIA protein, human
- Nfkbia protein, mouse
- Oligodeoxyribonucleotides
- Peptide Fragments
- myelin basic protein Ac1-11(4Y)
- myelin proteolipid protein (139-151)
- NF-KappaB Inhibitor alpha
- guanylyl-(3'-5')-guanosine
- Serine