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.
Kusakabe
K
K
Departments of Bacteriology, Internal Medicine, and Pathology, YokohamaCity University School of Medicine, Yokohama, Japan.
Xin
K Q
KQ
Katoh
H
H
Sumino
K
K
Hagiwara
E
E
Kawamoto
S
S
Okuda
K
K
Miyagi
Y
Y
Aoki
I
I
Nishioka
K
K
Klinman
D
D
Okuda
K
K
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000096:biosynthesis* / Q000235:genetics* / Q000276:immunology; D019302:HIV Envelope Protein gp160 / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D007115:Immunization Schedule; D007273:Injections, Intramuscular; D015847:Interleukin-4 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010957:Plasmids / Q000008:administration & dosage* / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology
D016915:AIDS Vaccines; D000914:Antibodies, Viral; D016207:Cytokines; D019302:HIV Envelope Protein gp160; D019444:Vaccines, DNA; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor