Anti-CD200R ameliorates collagen-induced arthritis in mice.
Immunization of DBA/1 with 100 microg bovine collagen type II emulsified in Freund's adjuvant, followed by booster injection in incomplete adjuvant at 18 days, leads to development of arthritis in more than 70% of mice by 28 days postinjection. We have previously shown that the novel immunosuppressant molecule CD200Fc (linking an extracellular domain of CD200 with a murine IgG2a Fc region) can suppress induction of disease when given to mice from the time of collagen injection. This occurs in concert with a decrease in the serum levels of anti-collagen IgG ( approximately 50% reduction), with relatively more IgG2b and IgG3, decreased serum levels of TNFalpha and IFN-gamma, and decreased production of those same cytokines after restimulation of lymphocytes in vitro with collagen. Since CD200 induces suppression following engagement of a receptor (CD200R), known to be expressed on, among other cells, macrophages, we investigated whether infusion of anti-CD200R and/or CD200Fc would ameliorate established disease in DBA mice, when injections were begun following collagen immunization. Our data indicate an arrest of disease following either treatment, with modification of a number of immune parameters (serum and lymphocyte cytokine production) consistent with a general role for CD200:CD200R interactions in the regulation of induction and/or expression of autoimmune disorders. When a higher dose (250 microg/mouse) of anti-CD200R was infused into a group of overtly arthritic mice, a significant ( approximately 50%) decrease in arthritic joint score occurred over the 4-week treatment period.
Gorczynski
Reginald M
RM
Transplant Research Division, The Toronto Hospital, 200 Elizabeth Street, Toronto, Ontario, M5G2C4, Canada.
Chen
Zhiqi
Z
Lee
Lydia
L
Yu
Kai
K
Hu
Jiang
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD; D000954:Antigens, Surface / Q000502:physiology*; D001168:Arthritis / Q000276:immunology / Q000517:prevention & control*; D001323:Autoantibodies / Q000096:biosynthesis; D003094:Collagen / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000209:etiology; D007141:Immunoglobulin Fc Fragments / Q000276:immunology / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D051379:Mice; D008811:Mice, Inbred DBA; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000954:Antigens, Surface; D001323:Autoantibodies; D007141:Immunoglobulin Fc Fragments; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D003094:Collagen; C042739:antigens, CD200