Int J Med Sci 2019; 16(5):741-750. doi:10.7150/ijms.31830

Research Paper

IFN-DC Loaded with Autophagosomes containing Virus Antigen is Highly Efficient in Inducing Virus-Specific Human T Cells

Jing Fan1*, Yinwei Wu1*, Mingchun Jiang2, Lili Wang1, Dandan Yin1, Yajuan Zhang4, Wei Ye1,2✉, Yongxiang Yi1,3

1. Clinical Research Center, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine. Zhong Fu Road, Gulou District, Nanjing, Jiangsu, PR China 210003.
2. Out-patient department, Nanjing Army Command College, Nanjing, 210045, China.
3. Liver Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine. Zhong Fu Road, Gulou District, Nanjing, Jiangsu, PR China 210003.
4. Department of Hepatobiliary Surgery, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine. Zhong Fu Road, Gulou District, Nanjing, Jiangsu, PR China 210003.
5. Health Management Center, Danyang People`s Hospital, Zhenjiang, 212300, China.
*These authors contributed equally to this work

Abstract

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<0.05) and CD8+ T cells (0.36 vs. 0.12%, p<0.05) to secrete IFN-γ compared with mIL-4-DC. Therefore, DRibbles containing specific viral antigens were efficient activators of human antigen-specific T cells. Our results demonstrated that IFN-DC loaded with CMV-DRibbles revealed a superior ability to induce CMV-specific T cells.

Keywords: autophagosome, cancer vaccine, cross-presentation, dendritic cells

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How to cite this article:
Fan J, Wu Y, Jiang M, Wang L, Yin D, Zhang Y, Ye W, Yi Y. IFN-DC Loaded with Autophagosomes containing Virus Antigen is Highly Efficient in Inducing Virus-Specific Human T Cells. Int J Med Sci 2019; 16(5):741-750. doi:10.7150/ijms.31830. Available from http://www.medsci.org/v16p0741.htm