Journal
VACCINE
Volume 32, Issue 35, Pages 4565-4570Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2014.06.039
Keywords
Hepatitis B virus; Dendritic cell; LIGHT; Cytotoxic T lymphocyte; Transgenic mice
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Funding
- National Natural Science Fund of China [81072459]
- Program for New Century Excellent Talents in University [NCET-12-0179]
- Shanghai Rising-Star Program [06QA14017]
- Science and Technology Commission of Shanghai Municipality [11DZ2260300]
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LIGHT, a TNF superfamily member (TNFSF14), is a type II transmembrane protein expressed on activated T cells and immature dendritic cells (DCs). However, the expression of LIGHT on mature DCs is down-regulated. Recent studies demonstrated that LIGHT provides potent costimulatory activity for T cells, enhancing proliferation and the production of Th1 cytokines independently of the B7-CD28 pathway. Here, we evaluated the effectiveness of peptide-pulsed DC-mediated antiviral immunity in HBV transgenic mice and the immunoadjuvant effect of LIGHT. The bone marrow-derived DCs were modified in vitro with an adenovirus (Ad) vector expressing mouse LIGHT (Ad-LIGHT), the expression of costimulatory molecules was up-regulated and the secretion of cytokines IL-12 and IFN-gamma increased. LIGHT-modified DCs enhanced allostimulation for T cells in mixed lymphocyte reaction (MLR). HBV peptide-pulsed DCs elicited HBV specific CD8+ T cell response and reduced the level of HBsAg and HBV DNA in sera of HBV transgenic mice. Importantly, LIGHT-modified DCs could induce stronger antiviral immunity. These results support the concept that genetic modification of DCs with a recombinant LIGHT adenovirus vector may be a useful strategy for antiviral immunotherapy. (C) 2014 Elsevier Ltd. All rights reserved.
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