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

• DOI: 10.1172/jci200319209
• Publication Date: 2003-11-04T01:45:38Z
• Authors: Zhongyu Liu; Xin Xu; Hui-Chen Hsu; Albert Tousson; Ping-Ar Yang; Qi Wu; Cunren Liu; Shaohua Yu; Huang-Ge Zhang; John D. Mountz
• Keywords: Fas ligand; Priming (agriculture)

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