Reference - Detail
|Author||Kusakabe K, Xin KQ, Katoh H, Sumino K, Hagiwara E, Kawamoto S, Okuda K, Miyagi Y, Aoki I, Nishioka K, Klinman D, Okuda K.|
|Title||The timing of GM-CSF expression plasmid administration influences the Th1/Th2 response induced by an HIV-1-specific DNA vaccine.|
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.
|MeSH||AIDS Vaccines / administration & dosage* AIDS Vaccines / immunology Amino Acid Sequence Animals Antibodies, Viral / biosynthesis Cell Movement / immunology Cells, Cultured Cytokines / administration & dosage Cytokines / genetics Cytokines / immunology Dendritic Cells / cytology Dendritic Cells / immunology Dendritic Cells / transplantation Female Flow Cytometry Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis* Granulocyte-Macrophage Colony-Stimulating Factor / genetics* Granulocyte-Macrophage Colony-Stimulating Factor / immunology HIV Envelope Protein gp160 / genetics HIV Envelope Protein gp160 / immunology HIV-1 / genetics HIV-1 / immunology* Immunization Schedule Injections, Intramuscular Interleukin-4 / administration & dosage Interleukin-4 / genetics Interleukin-4 / immunology Mice Mice, Inbred BALB C Molecular Sequence Data Plasmids / administration & dosage* Plasmids / immunology Th1 Cells / immunology* Th1 Cells / metabolism Th1 Cells / virology Th2 Cells / immunology* Th2 Cells / metabolism Th2 Cells / virology Vaccines, DNA / administration & dosage* Vaccines, DNA / immunology|
|Human and Animal Cells|