Abstract
The mechanism of immune activation induced by a plasmid-encoding GM-CSF (pGM-CSF), administered in combination with a DNA vaccine encoding the envelope of HIV, was studied. Injecting pGM-CSF i.m. into mice 3 days before DNA vaccination primarily induced a Th2 response. Simultaneous administration of the DNA vaccine plus pGM-CSF activated both a Th1 and a Th2 response. When the plasmid was injected 3 days after DNA vaccination, enhancement of Th1 immunity predominated. These results suggest that the timing of cytokine expression determines the phenotype of the resultant Th response. After 3 days of pGM-CSF injection, the increased percentages of CD11c+, CD8+ cells were observed in the regional lymph nodes. In addition, many infiltrated cells, including S-100 protein-positive cells, were found in the pGM-CSF-injected tissue. The importance of these S-100+ cells or both CD8+ and CD11c+ cells, especially that of dendritic cells (DCs), was also studied. DCs derived from bone marrow and cultured in RPMI 1640 medium containing IL-4 and GM-CSF were incubated with DNA vaccine and then transferred into naive mice. Mice receiving DCs showed strong HIV-1-specific Th2 immune responses. Our results suggest that DCs play important roles in the activation or modification of the Th2-type immune response induced by DNA vaccination.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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AIDS Vaccines / administration & dosage*
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AIDS Vaccines / immunology
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Amino Acid Sequence
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Animals
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Antibodies, Viral / biosynthesis
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Cell Movement / immunology
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Cells, Cultured
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Cytokines / administration & dosage
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Cytokines / genetics
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Cytokines / immunology
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Dendritic Cells / cytology
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Dendritic Cells / immunology
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Dendritic Cells / transplantation
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Female
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Flow Cytometry
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Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
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Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis*
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Granulocyte-Macrophage Colony-Stimulating Factor / genetics*
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Granulocyte-Macrophage Colony-Stimulating Factor / immunology
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HIV Envelope Protein gp160 / genetics
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HIV Envelope Protein gp160 / immunology
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HIV-1 / genetics
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HIV-1 / immunology*
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Immunization Schedule
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Injections, Intramuscular
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Interleukin-4 / administration & dosage
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Interleukin-4 / genetics
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Interleukin-4 / immunology
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Mice
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Mice, Inbred BALB C
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Molecular Sequence Data
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Plasmids / administration & dosage*
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Plasmids / immunology
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Th1 Cells / immunology*
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Th1 Cells / metabolism
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Th1 Cells / virology
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Th2 Cells / immunology*
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Th2 Cells / metabolism
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Th2 Cells / virology
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Vaccines, DNA / administration & dosage*
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Vaccines, DNA / immunology
Substances
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AIDS Vaccines
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Antibodies, Viral
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Cytokines
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HIV Envelope Protein gp160
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Vaccines, DNA
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Interleukin-4
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Granulocyte-Macrophage Colony-Stimulating Factor