The Role of Cd200/Cd200r Interactions in the Formation of Immunological Tolerance in Transplantation and Pregnancy

Abstract

The transmembrane CD200 glycoprotein belongs to the immunoglobulin family and it is widely represented on a variety of cell types, while its structurally similar CD200R receptor is expressed, mainly, on myeloid and lymphoid cells. An immunomodulatory role of CD200 and CD200R interaction is to activate the intracellular inhibitory cascade of reactions, leading to suppression of effector immune cells and attenuation of the inflammatory process. Thus, the CD200R activation stimulates the differentiation of naive T cells to regulatory T cells, increasing the indolamine 2,3-dioxygenase activity, and enhances the synthesis of IL-10 and TGF-β cytokines, contributing to development of a Th2-dependent anti-inflammatory environment. These immune regulatory events provide the development of immune tolerance and are required for controlling the development of autoimmune processes, hypersensitivity, engraftment of transplanted organs and tissues, as well as protecting the fetus from spontaneous abortion. Tolerogenic potential of interaction between CD200 and CD200R molecules can be effectively used for treatment of various diseases (e.g., Alzheimer’s, rheumatoid arthritis, allergies). In this review, we will address the role of CD200/CD200R interactions in stimulating the post-transplant engraftment and protecting a fetus from spontaneous abortion. Many in vivo and in vitro studies have suggested a key role of CD200/CD200R interaction in immune maintenance of both processes.