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.