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 language | English (US) |
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Pages (from-to) | 584-590 |
Number of pages | 7 |
Journal | Molecular Therapy |
Volume | 6 |
Issue number | 5 |
DOIs | |
State | Published - Nov 1 2002 |
Externally published | Yes |
Bibliographical note
Funding Information:We thank Imre Kovesdi (GenVec Corporation) for providing the Ad.FasL vector, and Joan Nash and Susan Schoonover for technical assistance. This work was supported in part by grants AR-6-2225 and DK44935 from the National Institutes of Health.
Keywords
- Arthritis
- Dendritic cells
- FasL
- Gene therapy
- Inflammation