Abstract
Single-stranded RNA oligonucleotides containing an immunostimulatory motif (immunostimulatory RNA [isRNA]) are potent inducers of interferon-alpha via the Toll-like receptor 7. We investigated the effect of isRNA on the development of an immune response. We show that isRNA activates dendritic cells and induces production of Th1-type cytokines both in vitro and in vivo. Cytokine production led to bystander activation of T and B cells. We further demonstrate that isRNA triggers the generation of antigen-specific cytotoxic T cells and of an IgG2a-biased antibody response to antigen in a sequence-dependent manner. In summary, we provide evidence for the first time that isRNA oligonucleotides can simultaneously activate the innate and adaptive arms of the immune system.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / genetics*
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Adjuvants, Immunologic / pharmacology*
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Animals
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Antigens
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Base Sequence
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Chickens
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Cytokines / biosynthesis
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Dendritic Cells / drug effects
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Dendritic Cells / immunology
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Female
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Immunity, Innate / drug effects
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Immunoglobulin G / biosynthesis*
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In Vitro Techniques
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Lymphocyte Activation / drug effects
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Oligoribonucleotides / chemistry
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Oligoribonucleotides / genetics*
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Oligoribonucleotides / immunology
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Oligoribonucleotides / pharmacology*
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Ovalbumin / immunology
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T-Lymphocytes, Cytotoxic / drug effects*
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T-Lymphocytes, Cytotoxic / immunology*
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Th1 Cells / drug effects
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Th1 Cells / immunology
Substances
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Adjuvants, Immunologic
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Antigens
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Cytokines
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Immunoglobulin G
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Oligoribonucleotides
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Ovalbumin