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Antigen-specific lymphocytes are involved in synovial proliferation within inflamed joints. Activated lymphocytes and synoviocytes from patients with rheumatoid arthritis express receptors that can bind TNF-related apoptosis-inducing ligand (TRAIL). A new study demonstrates that DCs pulsed with collagen and transduced with an adenovirus-based vector able to express TRAIL limit the incidence of arthritis in a model of collagen-induced arthritis and joint inflammation (see the related article beginning on page 1332). These results suggest that gene-modified cell therapy represents a therapeutic option for systemic rheumatic diseases.