CD200 immunoadhesin suppresses collagen-induced arthritis in mice.
DBA/1 mice immunized with 100 microg bovine collagen type II emulsified in Freund's adjuvant, followed by booster injection in incomplete adjuvant at 18 days, develop profound arthritis (>50% of animals) by 30 days postinjection. The molecule CD200 (previously called OX2), associated with, among others, follicular dendritic cells, is implicated in delivery of immunosuppressive signals to the immune system, and an immunoadhesin in which the extracellular domains of CD200 were linked to a mouse IgG2a Fc region has been shown to promote renal allograft survival. DBA/1 mice receiving 15 microg/mouse CD200Fc at 3-day intervals following immunization with collagen did not develop arthritis in this model. Lymphocytes taken from CD200Fc-treated, collagen-immunized mice produced significantly lower levels of TNFalpha and IFN-gamma in culture supernatants after restimulation in vitro with collagen, in contrast to cells taken from control mice treated with PBS or normal mouse Ig. Serum from CD200Fc-treated mice contained less anti-collagen IgG (approximately 50% reduction), with relatively more IgG2b and IgG3, and lower levels of TNFalpha and IFN-gamma, than control mice. These data indicate that this immunoadhesin may have a potent role to play in the regulation of autoimmune disorders.
Gorczynski
R M
RM
Transplant Research Division, The Toronto Hospital, 200 Elizabeth Street, Toronto, Ontario, M5G2C4, Canada.
Chen
Z
Z
Yu
K
K
Hu
J
J
D000818:Animals; D015703:Antigens, CD; D000954:Antigens, Surface / Q000276:immunology / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000276:immunology* / Q000517:prevention & control*; D015551:Autoimmunity; D002417:Cattle; D007141:Immunoglobulin Fc Fragments / Q000276:immunology / Q000627:therapeutic use; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D008811:Mice, Inbred DBA; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D015703:Antigens, CD; D000954:Antigens, Surface; D007141:Immunoglobulin Fc Fragments; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; C042739:antigens, CD200