In the November 3 issue of the Journal of Clinical Investigation, John Mountz and colleagues from the University of Alabama at Birmingham describe a gene-modified cell therapy utilizing the TRAIL molecule that successfully limits the incidence and severity of arthritis in a mouse model of collagen-induced arthritis and joint inflammation. The regime represents a therapeutic option for systemic rheumatic diseases.
Mountz and colleagues isolated dendritic cells prepared from either peripheral blood or bone marrow, which were then pulsed with collagen. The DNA of an adenovirus expressing tumor necrosis factorrelated apoptosis-inducing ligand (TRAIL) was then introduced into these cells. The design of the adenovirus vector allowed the researchers to "switch on" the expression of TRAIL by these gene-modified dendritic cells at their discretion, by the addition of doxycycline (DOX).
A cascade of immunological events including lymphocyte activation, lymphokine production, and proliferation of synovial cells (which comprise the loose connective tissue lining the joint cavity) is associated with collagen-induced arthritis in mice. Mountz and colleagues found that infusion of collagen-pulsed DOX-inducible TRAIL-expressing dendritic cells into these mice induced the apoptosis of collagen-specific T cells, a reduction in lymphokine production, and suppression of collagen-induced arthritis. The data suggest that this gene therapy regime is a safe and effective method for inhibiting the development of collagen-induced arthritis
In an accompanying commentary in the same issue, George and Maria Tsokos from the Walter Reed Army Institute of Research, Maryland, discuss how the results of Mountz and colleagues propose new possibilities for gene-modified cellbased treatment of rheumatoid arthritis.