CII-DC-AdTRAIL cell gene therapy inhibits infiltration of CII-reactive T cells and CII-induced arthritis.

Academic Article

Abstract

  • Previously, we described an APC-adenovirus (APC-Ad) FasL cell gene therapy method which could be used to deplete autoreactive T cells in vivo. FasL was toxic, however, and controlled regulation of FasL was not achieved. Here we describe an improved approach to delivering TNF-related apoptosis-inducing ligand (TRAIL) in vivo in which collagen II-induced (CII-induced) arthritis-susceptible (CIA-susceptible) DBA/1j mice were treated with CII-pulsed DCs that had been transfected with a novel Ad system. The Ad was engineered to exhibit inducible TRAIL under the control of the doxycycline-inducible (DOX-inducible) tetracycline response element (TRE). Four groups of mice were treated with CII-DC-AdTRAIL+DOX, CII-DC-AdTRAIL (no DOX), CII-DC-AdGFP+DOX, or DC-AdTRAIL+DOX (no CII), beginning 2 weeks after priming with CII in CFA. The incidence of arthritis and infiltration of T cells in the joint was significantly decreased in CII-DC-AdTRAIL+DOX-treated mice. The in vitro splenic T cell proliferative response and induction of IFN-gamma to bovine CII stimulation were also significantly reduced in mice treated with CII-DC-AdTRAIL+DOX. AdTRAIL+DOX was not toxic to DCs or mice but could induce activated T cells to undergo apoptosis in the spleen. Our results suggest that CII-DC-AdTRAIL+DOX cell gene therapy is a safe and effective method for inhibiting the development of CIA.
  • Published In

    Keywords

  • Adenoviridae, Animals, Antibodies, Antibody Formation, Apoptosis, Apoptosis Regulatory Proteins, Arthritis, Rheumatoid, Cell Movement, Cell- and Tissue-Based Therapy, Collagen Type II, Dendritic Cells, Doxorubicin, Female, Genetic Therapy, Lymphocyte Activation, Membrane Glycoproteins, Mice, Mice, Inbred DBA, Spleen, T-Lymphocytes, TNF-Related Apoptosis-Inducing Ligand, Transfection, Tumor Necrosis Factor-alpha
  • Digital Object Identifier (doi)

    Pubmed Id

  • 23431076
  • Author List

  • Liu Z; Xu X; Hsu H-C; Tousson A; Yang P-A; Wu Q; Liu C; Yu S; Zhang H-G; Mountz JD
  • Start Page

  • 1332
  • End Page

  • 1341
  • Volume

  • 112
  • Issue

  • 9