The Timing of GM-CSF Expression Plasmid Administration Influences the Th1/Th2 Response Induced by an HIV-1-Specific DNA Vaccine
| Autor: | Kenji Okuda, Ken-ichi Kusakabe, Ichiro Aoki, Susumu Kawamoto, Eri Hagiwara, Hidenori Katoh, Dennis M. Klinman, Katsuji Okuda, Kusuya Nishioka, Kaharu Sumino, Ke-Qin Xin, Yohei Miyagi |
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| Rok vydání: | 2000 |
| Předmět: |
Molecular Sequence Data
Immunology CD11c Biology Antibodies Viral Injections Intramuscular HIV Envelope Protein gp160 DNA vaccination Mice Th2 Cells Plasmid Immune system Cell Movement Vaccines DNA medicine Animals Immunology and Allergy Amino Acid Sequence Cells Cultured Immunization Schedule AIDS Vaccines Mice Inbred BALB C Expression vector Granulocyte-Macrophage Colony-Stimulating Factor Dendritic Cells Th1 Cells Flow Cytometry Molecular biology medicine.anatomical_structure HIV-1 Cytokines Female Interleukin-4 Bone marrow Lymph CD8 Plasmids |
| Zdroj: | The Journal of Immunology. 164:3102-3111 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.164.6.3102 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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