Modulation of CD200 receptors as a novel method of immunosuppression

Abstract

Current methods of therapeutic immunomodulation are unsatisfactory. More effective and safer strategies are needed either to suppress immune responses for the treatment of transplant rejections, autoimmunity and allergy or to boost immunity against infectious diseases and cancer. This patent application proposes a novel approach towards these goals based on targeting CD200 receptors (CD200R). Whereas CD200 is expressed on lymphoid cells, neurons and endothelium, CD200R are mainly expressed on macrophages and myeloid cells. Crosslinking CD200R with CD200:Fc, an immunoadhesin made up of the CD200 extracellular region fused to the murine IgG2a Fc region or with anti-CD200R monoclonal antibodies (mAbs) can prolong allograft and xenograft survival and ameliorate collagen-induced arthritis in mice. Murine CD200R isoforms were identified by genomic analyses and partially characterised using specific mAbs acting presumably as receptor agonists. Myeloid dendritic cells (DCs) generated in the presence of anti-CD200R isoform mAbs were unable to stimulate the production of IFN-γ and cytolytic lymphocytes in a mixed lymphocyte culture but induced the emergence of suppressor cells. When injected prior to transplantation, such DCs were capable of significantly prolonging skin allograft survival. Although the data suggest that CD200R might serve to dampen immune responses, further investigations are required to determine whether this approach would be applicable to human disease situations.

• CD200
• CD200 receptors (CD200R)
• collagen-induced arthritis
• dendritic cell
• immunoregulation
• immunosuppression
• transplant rejection