27 May 2019
Global reach, higher impact
Int J Med Sci 2019; 16(5):741-750. doi:10.7150/ijms.31830
IFN-DC Loaded with Autophagosomes containing Virus Antigen is Highly Efficient in Inducing Virus-Specific Human T Cells
1. Clinical Research Center, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine. Zhong Fu Road, Gulou District, Nanjing, Jiangsu, PR China 210003.
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