IFN-DC Loaded with Autophagosomes containing Virus Antigen is Highly Efficient in Inducing Virus-Specific Human T Cells
| Autor: | Mingchun Jiang, Yinwei Wu, Yajuan Zhang, Wei Ye, Jing Fan, Dandan Yin, Lili Wang, Yongxiang Yi |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Gene Expression Regulation
Viral T-Lymphocytes Interleukin-1beta autophagosome CD11c Blood Donors Cancer Vaccines Viral Matrix Proteins 03 medical and health sciences 0302 clinical medicine Virus antigen Immune system Antigen Cell Line Tumor Autophagy Humans cross-presentation CD86 Interleukin-6 Chemistry Autophagosomes Cross-presentation Dendritic Cells General Medicine Interleukin-10 Cell biology Gene Expression Regulation Neoplastic 030211 gastroenterology & hepatology Interleukin-4 cancer vaccine CD8 CD80 Research Paper |
| Zdroj: | International Journal of Medical Sciences |
| ISSN: | 1449-1907 |
| DOI: | 10.7150/ijms.31830 |
| Popis: | Autophagy plays a critical role in the regulation of innate and adaptive immune responses to pathogens and tumors. A previous study utilized proteasome and lysosome inhibitors to form autophagosomes (DRibbles) and the effect of dendritic cells (DCs) loaded with DRibbles in activating antigen-specific T cells has been demonstrated in a mouse experiment and human IL-4-DC. In this study, CMV-DRibbles derived from MDA cell lines expressing cytomegalovirus (CMV) pp65 protein were loaded onto human IFN-DC and IL-4-DC derived from monocytes, respectively. We observed that CMV-DRibbles resulted in the up-regulation of HLA-DR, CD11c, and CD83, but not co-stimulatory molecules CD 80 and CD86 on IFN-DC. Meanwhile, the expression of HLA-DR, CD80, CD83, and CD86, except for CD11c on IL-4-DC loaded with CMV-DRibbles were up-regulated. Moreover, CMV-DRibbles had no ability to stimulate these two moDCs to secrete cytokines IL-6, IL-1β and IL-10. Then, we optimized the conditions for antigen up-take by DCs and found that mature moDCs had a superior ability to up-take CMV-DRibbles compared with immature DCs in a dose-dependent manner. Furthermore, the efficiency of CMV-DRibbles up-take by IFN-DC was superior compared to IL-4-DC. Finally, we observed that mIFN-DC was significantly more efficient at stimulating autologous CMV-specific CD4+ T cells (0.39 vs. 0.28 %, p |
| Databáze: | OpenAIRE |
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