The Same Immunoregulatory Molecules Contribute to Successful Pregnancy and Transplantation

Abstract

Regulation of CD200 and MD-1 expression may control both pregnancy and allograft survival.

CD200 Is a Ligand for All Members of the CD200R Family of Immunoregulatory Molecules

“…Other data suggest a key role for CD200-CD200R interactions in regulating acquired immunity: transplant rejection (3), autoimmunity (4,6,7), and fetal loss (17). An intracellular signaling role for CD200R in this interaction was predicted from structural analysis of the CD200 molecule, showing that it lacked signaling domains in the cytoplasmic tail or "docking motifs" within membrane-spanning regions, and was confirmed in several independent structural and functional studies (3,4,8).…”

Enhanced tryptophan catabolism in the absence of the molecular adapter DAP12

“…A novel concept emerging from studies on immunomodulation is that the same cells [30], molecules [31] and mechanisms [15] mediate Ag-specific unresponsiveness under a variety of apparently disparate conditions. Although only one of several modes of tolerance induction, the immunosuppressive pathway of tryptophan catabolism has been shown to contribute to successful pregnancy [32] and transplantation [33][34][35], as well as to effective control of autoimmunity [14,16,36].…”

CD200-dependent and nonCD200-dependant pathways of NK cell suppression by human IVIG

“…CD200 is a tolerance signaling molecule expressed on a variety of cells including activated T and B cells, brain cells, and fetal trophoblasts, and acts by binding to CD200 receptors [8,9]. This binding results in generation of different types of immunoregulatory suppressor T cells, including CD4 + 25 + Treg cells, and activation of indoleamine 2,3-dioxygenase production in myeloid cells [10,11]. When murine or human lymphocytic cells are stored at 4°C overnight, cell surface CD200 is lost and activity blocking anti-CD200 binding to fresh cells is present in conditioned supernatant [7].…”