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

Seon Hee Kim, Sunyoung Kim, Thomas J. Oligino, Paul D. Robbins

Research output: Contribution to journalArticle

83 Scopus citations

Abstract

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-γ (IFN-γ) 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.

Original languageEnglish (US)
Pages (from-to)584-590
Number of pages7
JournalMolecular Therapy
Volume6
Issue number5
DOIs
StatePublished - Nov 1 2002
Externally publishedYes

Keywords

  • Arthritis
  • Dendritic cells
  • FasL
  • Gene therapy
  • Inflammation

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