التفاصيل البيبلوغرافية
| العنوان: |
Cross-presentation of viral antigens in dribbles leads to efficient activation of virus-specific human memory t cells |
| المؤلفون: |
Ye, Wei, Xing, Yun, Paustian, Christopher, van de Ven, Rieneke, Moudgil, Tarsem, Hilton, Traci L, Fox, Bernard A, Urba, Walter J, Zhao, Wei, Hu, Hong-Ming |
| بيانات النشر: |
BioMed Central Ltd. |
| سنة النشر: |
2014 |
| المجموعة: |
BioMed Central |
| مصطلحات موضوعية: |
Autophagosome, Cross-presentation, Immunological monitoring, Immunotherapy biomarker, Viral vaccine, Cancer vaccine, Memory antigen-specific T cells, Proteasome |
| الوصف: |
Background Autophagy regulates innate and adaptive immune responses to pathogens and tumors. We have reported that autophagosomes derived from tumor cells after proteasome inhibition, DRibbles (Defective ribosomal products in blebs), were excellent sources of antigens for efficient cross priming of tumor-specific CD8 + T cells, which mediated regression of established tumors in mice. But the activity of DRibbles in human has not been reported. Methods DRibbles or cell lysates derived from HEK293T or UbiLT3 cell lines expressing cytomegalovirus (CMV) pp65 protein or transfected with a plasmid encoding dominant HLA-A2 restricted CMV, Epstein-Barr virus (EBV), and Influenza (Flu) epitopes (CEF) were loaded onto human monocytes or PBMCs and the response of human CMV pp65 or CEF antigen-specific CD4 + and CD8 + memory T cells was detected by intracellular staining. The effect of cytokines (GM-CSF, IL-4, IL-12, TNF-α, IFN-α and IFN-γ) TLR agonists (Lipopolysaccharide, Polyinosinic-polycytidylic acid (poly(I:C), M52-CpG, R848, TLR2 ligand) and CD40 ligand on the cross-presentation of antigens contained in DRibbles or cell lysates was explored. Results In this study we showed that purified monocytes, or human PBMCs, loaded with DRibbles isolated from cells expressing CMV or CEF epitopes, could activate CMV- or CEF-specific memory T cells. DRibbles were significantly more efficient at stimulating CD8 + memory T cells compared to cell lysates expressing the same antigenic epitopes. We optimized the conditions for T-cell activation and IFN-γ production following direct loading of DRibbles onto PBMCs. We found that the addition of Poly(I:C), CD40 ligand, and GM-CSF to the PBMCs together with DRibbles significantly increased the level of CD8 + T cell responses. Conclusions DRibbles containing specific viral antigens are an efficient ex vivo activator of human antigen-specific memory T cells specific for those antigens. This function could be enhanced by combining with Poly(I:C), CD40 ligand, and GM-CSF. This study ... |
| نوع الوثيقة: |
report |
| اللغة: |
English |
| العلاقة: |
http://www.translational-medicine.com/content/12/1/100Test |
| الإتاحة: |
http://www.translational-medicine.com/content/12/1/100Test |
| حقوق: |
Copyright 2014 Ye et al.; licensee BioMed Central Ltd. |
| رقم الانضمام: |
edsbas.654646EA |
| قاعدة البيانات: |
BASE |
