- Paper Report
- Open Access
OX40/OX40L in RA
- John Isaacs1
© Current Science Ltd 2000
- Published: 19 October 2000
- Collagen arthritis
OX40, a tumor necrosis factor receptor (TNFR) family member on activated T cells, binds OX40L, a TNF family member on B cells, dendritic cells and endothelium. Their interaction provides T- and B-cell costimulation with T-cell activation and B-cell antibody production. Endothelial adhesion of activated T-cells and activation of dendritic cells may also result. This study investigated their role in inflammatory arthritis.
OX40L monoclonal antibody abrogated murine collagen-induced arthritis (CIA) when administered for 4 days from boosting immunisation but not if administered 7 days later. Serum IgG2a anti-collagen titres were specifically reduced; in vitro, T-cell proliferation in response to collagen was maintained, but a-interferon production was inhibited.
Rheumatoid arthritis synovial fluid T cells but not peripheral blood T cells expressed OX40, and OX40L was present on synovial sublining cells.
The authors conclude that OX40/OX40L interaction is not necessary for T-cell activation but enhances Th1 responses. The therapeutic effect of blockade may represent a reduced Th1 response, but also perhaps reduced migration of activated T cells to the joint.
Collagen arthritis, blocking studies, proliferation assays, anti-collagen titres, immunohistochemistry