Advertisement

Research Article Free access | 10.1172/JCI119726

Amelioration of collagen-induced arthritis by CD95 (Apo-1/Fas)-ligand gene transfer.

H Zhang, Y Yang, J L Horton, E B Samoilova, T A Judge, L A Turka, J M Wilson, and Y Chen

Institute for Human Gene Therapy, Department of Molecular and Cellular Engineering, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.

Find articles by Zhang, H. in: PubMed | Google Scholar

Institute for Human Gene Therapy, Department of Molecular and Cellular Engineering, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.

Find articles by Yang, Y. in: PubMed | Google Scholar

Institute for Human Gene Therapy, Department of Molecular and Cellular Engineering, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.

Find articles by Horton, J. in: PubMed | Google Scholar

Institute for Human Gene Therapy, Department of Molecular and Cellular Engineering, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.

Find articles by Samoilova, E. in: PubMed | Google Scholar

Institute for Human Gene Therapy, Department of Molecular and Cellular Engineering, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.

Find articles by Judge, T. in: PubMed | Google Scholar

Institute for Human Gene Therapy, Department of Molecular and Cellular Engineering, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.

Find articles by Turka, L. in: PubMed | Google Scholar

Institute for Human Gene Therapy, Department of Molecular and Cellular Engineering, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.

Find articles by Wilson, J. in: PubMed | Google Scholar

Institute for Human Gene Therapy, Department of Molecular and Cellular Engineering, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.

Find articles by Chen, Y. in: PubMed | Google Scholar

Published October 15, 1997 - More info

Published in Volume 100, Issue 8 on October 15, 1997
J Clin Invest. 1997;100(8):1951–1957. https://doi.org/10.1172/JCI119726.
© 1997 The American Society for Clinical Investigation
Published October 15, 1997 - Version history
View PDF
Abstract

Both rheumatoid arthritis and animal models of autoimmune arthritis are characterized by hyperactivation of synovial cells and hyperplasia of the synovial membrane. The activated synovial cells produce inflammatory cytokines and degradative enzymes that lead to destruction of cartilage and bones. Effective treatment of arthritis may require elimination of most or all activated synovial cells. The death factor Fas/Apo-1 and its ligand (FasL) play pivotal roles in maintaining self-tolerance and immune privilege. Fas is expressed constitutively in most tissues, and is dramatically upregulated at the site of inflammation. In both rheumatoid arthritis and animal models of autoimmune arthritis, high levels of Fas are expressed on activated synovial cells and infiltrating leukocytes in the inflamed joints. Unlike Fas, however, the levels of FasL expressed in the arthritic joints are extremely low, and most activated synovial cells survive despite high levels of Fas expression. To upregulate FasL expression in the arthritic joints, we have generated a recombinant replication-defective adenovirus carrying FasL gene; injection of the FasL virus into inflamed joints conferred high levels of FasL expression, induced apoptosis of synovial cells, and ameliorated collagen-induced arthritis in DBA/1 mice. The Fas-ligand virus also inhibited production of interferon-gamma by collagen-specific T cells. Coadministration of Fas-immunoglobulin fusion protein with the Fas-ligand virus prevented these effects, demonstrating the specificity of the Fas-ligand virus. Thus, FasL gene transfer at the site of inflammation effectively ameliorates autoimmune disease.

Version history
  • Version 1 (October 15, 1997): No description
Advertisement
Advertisement