RRC ID 12175
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.
Journal J Immunol
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.
Volume 164(6)
Pages 3102-11
Published 2000-3-15
DOI 10.4049/jimmunol.164.6.3102
PII ji_v164n6p3102
PMID 10706700
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
IF 4.886
Times Cited 110
DNA material pCAmTNF alpha Expresses the mouse TNF alpha gene in mammalian cells (RDB01510)