Abstract
IL-23 is a heterodimeric cytokine consisting of p19 and the p40 subunit of IL-12. IL-23 has been shown to possess IL-12-like biological activities, but is different in its capacity to stimulate memory T cells in vitro. In this study, we investigated whether IL-23 could influence envelope protein 2 (E2)-specific cell-mediated immunity induced by immunization of hepatitis C virus E2 DNA. We found that IL-23 induced long-lasting Th1 and CTL immune responses to E2, which are much stronger than IL-12-mediated immune responses. Interestingly, IL-23N220L, an N-glycosylation mutant showing reduced expression of excess p40 without changing the level of IL-23, exhibited a higher ratio of IFN-gamma- to IL-4-producing CD4(+) T cell frequency than did wild-type IL-23, suggesting a negative regulatory effect of p40 on Th1-prone immune response induced by IL-23. These data suggest that IL-23, particularly IL-23N220L, would be an effective adjuvant of DNA vaccine for the induction of durable Ag-specific T cell immunity.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / administration & dosage*
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Adjuvants, Immunologic / genetics
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Adjuvants, Immunologic / therapeutic use
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Amino Acid Sequence
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Animals
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Cytotoxicity, Immunologic / genetics
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Female
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Genetic Vectors
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Hepacivirus / genetics
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Hepacivirus / immunology*
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Humans
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Immunity, Cellular / genetics
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Injections, Intramuscular
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Interleukin-12 / administration & dosage*
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Interleukin-12 / genetics
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Interleukin-12 / therapeutic use
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Interleukin-12 Subunit p40
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Interleukin-23
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Interleukin-23 Subunit p19
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Interleukins / administration & dosage*
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Interleukins / genetics
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Interleukins / therapeutic use
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Mice
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Mice, Inbred BALB C
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Molecular Sequence Data
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Protein Subunits / administration & dosage
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T-Lymphocytes, Cytotoxic / immunology*
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T-Lymphocytes, Cytotoxic / virology
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Th1 Cells / immunology*
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Th1 Cells / virology
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Vaccines, DNA / administration & dosage
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Vaccines, DNA / genetics
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Vaccines, DNA / immunology*
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Viral Envelope Proteins / administration & dosage
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Viral Envelope Proteins / genetics
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Viral Envelope Proteins / immunology*
Substances
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Adjuvants, Immunologic
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IL23A protein, human
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Il23a protein, mouse
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Interleukin-12 Subunit p40
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Interleukin-23
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Interleukin-23 Subunit p19
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Interleukins
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Protein Subunits
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Vaccines, DNA
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Viral Envelope Proteins
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glycoprotein E2, Hepatitis C virus
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Interleukin-12