title: Blockade of B7-H1 enhances dendritic cell-mediated T cell response and antiviral immunity in HBV transgenic mice.
abstract: Dendritic cells (DCs) have been identified as the most effective antigen-presenting cell (APC), much attention has been directed toward the use of DCs in vaccine strategies for the treatment of cancer or chronic virus infection. B7-H1 (PD-L1) is a ligand for programmed cell death-1 (PD-1) and does not bind to other CD28 family members, it is expressed on resting and upregulated on activated B, T, myeloid, and dendritic cells (DCs). The overwhelming number of studies supports the role of B7-H1 as a negative regulator of T cell responses. RNA interference (RNAi) is a mechanism for sequence-specific posttranscriptional inhibition of gene expression via double stranded RNA molecules and it has recently been applied to mammalian cells with the use of small interfering RNAs (siRNAs). In the study, transfection of DCs with siRNA specific for B7-H1 gene resulted in the blockade of the expression of B7-H1 on DCs. The allostimulatory activity of DCs could be enhanced by silencing of B7-H1 on DCs. Blockade of B7-H1 on DCs inhibited the production of IFN-γ and IL-10 but not IL-2 and IL-4 in mixed lymphocyte reaction (MLR). HBV specific peptide-pulsed DCs could break tolerance and trigger specific CTL responses, the level of HBsAg and HBV DNA in sera of HBV transgenic mice decreased, whereas blockade of B7-H1 on DCs augmented the effects. These data strongly support the concept that blockade of B7-H1 can enhance DC-mediated antiviral immune responses.
authors: School of Life Science, East China Normal University, Shanghai 200062, China. wzjiang@bio.ecnu.edu.cn
authors: Wenzheng
authors: W
authors: Jiang
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors*; D004279:DNA, Viral / Q000097:blood; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D020868:Gene Silencing; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D034741:RNA, Small Interfering; D016753:Interleukin-10; D007371:Interferon-gamma