Cytolytic DNA vaccine encoding lytic perforin augments the maturation of- and antigen presentation by- dendritic cells in a time-dependent manner
| Autor: | Wenbo Yu, John D. Hayball, Kerrilyn R. Diener, Ilia Voskoboinik, Eric J. Gowans, Branka Grubor-Bauk, Danushka K. Wijesundara, Preethi Eldi, Ben J. C. Quah |
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| Přispěvatelé: | Wijesundara, Danushka K, Yu, Wenbo, Quah, Ben JC, Eldi, Preethi, Hayball, John D, Diener, Kerrilyn R, Voskoboinik, Ilia, Gowans, Eric J, Grubor-Bauk, Branka |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Time Factors Science T cell Antigen presentation T cells Priming (immunology) chemical and pharmacologic phenomena Article DNA vaccination 03 medical and health sciences plasmid DNA 0302 clinical medicine Vaccines DNA medicine Animals Humans dendritic cells Antigens cytomegalovirus self-antigens Cell Proliferation CD86 Antigen Presentation Multidisciplinary biology Perforin Dendritic Cells Molecular biology Multidisciplinary Sciences Mice Inbred C57BL cytolytic DNA immunisation HEK293 Cells 030104 developmental biology medicine.anatomical_structure Lytic cycle biology.protein Medicine CD80 B lymphocytes T-Lymphocytes Cytotoxic 030215 immunology |
| Zdroj: | Scientific Reports, Vol 7, Iss 1, Pp 1-8 (2017) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-017-08063-1 |
| Popis: | The use of cost-effective vaccines capable of inducing robust CD8+ T cell immunity will contribute significantly towards the elimination of persistent viral infections and cancers worldwide. We have previously reported that a cytolytic DNA vaccine encoding an immunogen and a truncated mouse perforin (PRF) protein significantly augments anti-viral T cell (including CD8+ T cell) immunity. Thus, the current study investigated whether this vaccine enhances activation of dendritic cells (DCs) resulting in greater priming of CD8+ T cell immunity. In vitro data showed that transfection of HEK293T cells with the cytolytic DNA resulted in the release of lactate dehydrogenase, indicative of necrotic/lytic cell death. In vitro exposure of this lytic cell debris to purified DCs from naïve C57BL/6 mice resulted in maturation of DCs as determined by up-regulation of CD80/CD86. Using activation/proliferation of adoptively transferred OT-I CD8+ T cells to measure antigen presentation by DCs in vivo, it was determined that cytolytic DNA immunisation resulted in a time-dependent increase in the proliferation of OT-I CD8+ T cells compared to canonical DNA immunisation. Overall, the data suggest that the cytolytic DNA vaccine increases the activity of DCs which has important implications for the design of DNA vaccines to improve their translational prospects. |
| Databáze: | OpenAIRE |
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