The timing of GM-CSF expression plasmid administration influences the Th1/Th2 response induced by an HIV-1-specific DNA vaccine.

Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.

The timing of GM-CSF expression plasmid administration influences the Th1/Th2 response induced by an HIV-1-specific DNA vaccine.

J Immunol. 2000 Mar 15;164(6):3102-11. Unique Identifier : AIDSLINE MED/20171510
Kusakabe K; Xin KQ; Katoh H; Sumino K; Hagiwara E; Kawamoto S; Okuda K; Miyagi Y; Aoki I; Nishioka K; Klinman D; Okuda K; Departments of Bacteriology, Internal Medicine, and Pathology,; YokohamaCity University School of Medicine, Yokohama, Japan.

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.

Keywords: JOURNAL ARTICLE Amino Acid Sequence Animal Antibodies, Viral/BIOSYNTHESIS AIDS Vaccines/*ADMINISTRATION & DOSAGE/IMMUNOLOGY Cell Movement/IMMUNOLOGY Cells, Cultured Cytokines/ADMINISTRATION & DOSAGE/GENETICS/IMMUNOLOGY Dendritic Cells/CYTOLOGY/IMMUNOLOGY/TRANSPLANTATION Female Flow Cytometry Granulocyte-Macrophage Colony-Stimulating Factor/ADMINISTRATION & DOSAGE/*BIOSYNTHESIS/*GENETICS/IMMUNOLOGY HIV Envelope Protein gp160/GENETICS/IMMUNOLOGY HIV-1/GENETICS/*IMMUNOLOGY Immunization Schedule Injections, Intramuscular Interleukin-4/ADMINISTRATION & DOSAGE/GENETICS/IMMUNOLOGY Mice Mice, Inbred BALB C Molecular Sequence Data Plasmids/*ADMINISTRATION & DOSAGE/IMMUNOLOGY Support, Non-U.S. Gov't Th1 Cells/*IMMUNOLOGY/METABOLISM/VIROLOGY Th2 Cells/*IMMUNOLOGY/METABOLISM/VIROLOGY Vaccines, DNA/*ADMINISTRATION & DOSAGE/IMMUNOLOGY

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