Prevention of collagen-induced arthritis with an antibody to gp39, the ligand for CD40.
The ligand for the CD40 antigen is a 39-kilodalton protein, gp39, expressed on the surface of activated CD4+ T cells and is essential for thymus-dependent humoral immunity. The role of gp39-CD40 interactions in autoimmune disease was investigated in vivo with the use of an antibody that blocks their interactions (anti-gp39). Arthritis induced in mice by immunization with type II collagen was inhibited by anti-gp39. Anti-gp39 blocked the development of joint inflammation, serum antibody titers to collagen, the infiltration of inflammatory cells into the subsynovial tissue, and the erosion of cartilage and bone. Thus, interference with gp39-CD40 interactions may have therapeutic potential in the treatment of autoimmune disease.
Durie
F H
FH
Department of Microbiology, Dartmouth Medical School, Lebanon, NH 03756.
Fava
R A
RA
Foy
T M
TM
Aruffo
A
A
Ledbetter
J A
JA
Noelle
R J
RJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D019013:CD40 Antigens; D023201:CD40 Ligand; D003094:Collagen / Q000276:immunology; D004195:Disease Models, Animal; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D007596:Joints / Q000473:pathology; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000945:Antigens, Differentiation, T-Lymphocyte; D019013:CD40 Antigens; D007074:Immunoglobulin G; D008024:Ligands; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D003094:Collagen