Effective treatment of established mouse collagen-induced arthritis by systemic administration of dendritic cells genetically modified to express FasL

Mol Ther. 2002 Nov;6(5):584-90.


Previous reports have demonstrated the ability of antigen-presenting cells (APCs), genetically modified to express Fas ligand (FasL), to inhibit T-cell responses through the induction of apoptosis of antigen-specific T cells. Here we have examined the ability of primary mouse bone marrow-derived dendritic cells (DCs), genetically modified by adenoviral infection to express FasL, to inhibit progression of established collagen-induced arthritis (CIA) in DBA/1 mice. Systemic injection of DC/FasL into mice with established CIA resulted in substantial disease amelioration as determined by analysis of paw swelling, arthritic index, and number of arthritic paws. Moreover, a single injection of DC/FasL resulted in extended suppression of disease. We also demonstrate that treatment of arthritic mice with DC/FasL suppressed interferon-gamma (IFN-gamma) production from spleen-derived lymphocytes and reduced T-cell proliferation following collagen stimulation without affecting the levels of anti-collagen antibody isotypes. These results demonstrate that systemic administration of DC/FasL is able to suppress collagen-reactive T cells, resulting in effective and sustained treatment of established CIA.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arthritis / therapy*
  • Cell Division
  • Collagen / pharmacology*
  • Cytokines / metabolism
  • Dendritic Cells / metabolism*
  • Disease Models, Animal
  • Fas Ligand Protein
  • Female
  • Flow Cytometry
  • Genetic Therapy / methods*
  • Genetic Vectors
  • Interferon-gamma / metabolism
  • Male
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred DBA
  • Spleen / cytology
  • T-Lymphocytes / metabolism
  • Time Factors


  • Cytokines
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Membrane Glycoproteins
  • Interferon-gamma
  • Collagen