The ligand for the CD40 antigen is a 39-kilodalton protein, gp39, expr
essed on the surface of activated CD4+ T cells and is essential for th
ymus-dependent humoral immunity. The role of gp39-CD40 interactions in
autoimmune disease was investigated in vivo with the use of an antibo
dy that blocks their interactions (anti-gp39). Arthritis induced in mi
ce by immunization with type II collagen was inhibited by anti-gp39. A
nti-gp39 blocked the development of joint inflammation, serum antibody
titers to collagen, the infiltration of inflammatory cells into the s
ubsynovial tissue, and the erosion of cartilage and bone. Thus, interf
erence with gp39-CD40 interactions may have therapeutic potential in t
he treatment of autoimmune disease.