CII-DC-AdTRAIL cell gene therapy inhibits infiltration of CII-reactive T cells and CII-induced arthritis
Zhongyu Liu, … , Huang-Ge Zhang, John D. Mountz
Zhongyu Liu, … , Huang-Ge Zhang, John D. Mountz
Published November 1, 2003
Citation Information: J Clin Invest. 2003;112(9):1332-1341. https://doi.org/10.1172/JCI19209.
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Article Genetics

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

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-γ 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.

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

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CII-DC-AdTRAIL+DOX treatment partly decreased production of anti-CII Ab....
CII-DC-AdTRAIL+DOX treatment partly decreased production of anti-CII Ab. The level of anti-CII Ab in the sera of mice receiving different treatments was measured by an ELISA assay. CII arthritis was induced in DBA/1j mice, and different groups of mice were treated with CII-DC-AdTRAIL+DOX, CII-DC-AdTRAIL (no DOX), CII-DC-AdGFP+DOX, or DC-AdTRAIL+DOX. The sera were collected at the time of sacrifice (19 weeks of age), and an ELISA assay was performed. CII-DC-AdTRAIL+DOX treatment significantly inhibited the sera level of CII Ab in mice. Each bar represents the mean of the level of CII Ab from ten mice in each treatment group. **P < 0.01.