Recombinant adenovirus expressing ICP47 gene suppresses the ability of dendritic cells by restricting specific T cell responses

Cell Immunol. 2013 Apr;282(2):129-35. doi: 10.1016/j.cellimm.2013.05.004. Epub 2013 May 22.

Abstract

Adenoviral vectors have been demonstrated to be one of the most effective vehicles to deliver foreign DNA into dendritic cells (DCs). However, the response of host immune systems against foreign gene products is a major obstacle to successful gene therapy. Infected cell protein 47 (ICP47) inhibits MHC Ⅰ antigen presentation pathway by binding to host transporter associated with antigen presentation (TAP), and thereby attenuates of specific cytotoxic T lymphocytes (CTLs) responses and evades the host immune clearance. This subject was designed to construct a recombinant adenovirus expressing His-tag-ICP47 fusion protein to investigate further the role of ICP47 in the elimination of transgene expression. Consequently, a recombinant adenovirus expressing the His-tag-ICP47 fusion protein was successfully constructed and it had the abilities of attenuating the stimulatory capacity of DCs by reducing the proliferation of lymphocytes and cytokine production of perforin compared with those of the r-track group and the control group. Our observations provide the first evidence of the regulation mechanism of ICP47 on DC-based immunotherapy for long-term persistence.

Keywords: Dendritic cells; ICP47; Recombinant adenovirus; Stimulatory capacity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Blotting, Western
  • Cell Proliferation
  • Cytokines / immunology
  • Cytokines / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Flow Cytometry
  • Genetic Vectors / genetics
  • Humans
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / immunology*
  • Immediate-Early Proteins / metabolism
  • Lymphocyte Activation / immunology
  • Lymphocyte Culture Test, Mixed
  • Lymphocytes / immunology
  • Lymphocytes / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / metabolism
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism
  • Transgenes / genetics
  • Transgenes / immunology
  • Viral Proteins / genetics
  • Viral Proteins / immunology*
  • Viral Proteins / metabolism

Substances

  • Cytokines
  • ICP47 protein, Herpes simplex virus
  • Immediate-Early Proteins
  • Recombinant Fusion Proteins
  • Viral Proteins