OX40 ligand (OX40L) and OX40 (CD134) are a pair of cell surface molecules b
elonging to the TNF/TNF receptor family. Interaction of OX40L with its rece
ptor OX40 is thought to be important in T cell activation through T cell/an
tigen-presenting cell interaction. However, involvement of these molecules
in the pathogenesis of rheumatoid arthritis (RA) remains unclear. To explor
e the contribution of OX40/OX40L interaction to the pathogenesis of RA in v
ivo, we evaluated the effect of a neutralizing anti-OX40L monoclonal antibo
dy (mAb) on the development of collagen-induced arthritis (CIA) in DBA/1 mi
ce as an animal model for RA. Administration of anti-OX40L mAb into type II
collagen (CII) -immunized DBA/1 mice dramatically ameliorated the disease
severity. In vivo treatment with anti-OX40L mAb did not inhibit the expansi
on of CII-reactive T cells, but suppressed IFN-gamma and anti-CII IgG2a pro
duction. Therefore, OX40/OX40L interaction appears to play a critical role
in the development of CIA by enhancing Th1-type autoimmune response. In add
ition, T lymphocytes in synovial fluid and synovial tissue from RA patients
expressed OX40, while OX40L was expressed on sublining cells in synovial t
issue. These results indicate that OX40/OX40L interaction may play a critic
al role in the development of RA.