Is the CD200/CD200 receptor interaction more than just a myeloid cell inhibitory signal?

The membrane glycoprotein CD200, which has a widespread but defined distribution and a structurally similar receptor (CD200R) that transmits an inhibitory signal to cells of the hematopoetic lineage, especially myeloid cells, has been characterized. CD200R expression is restricted predominantly to cells of the myeloid lineage indicating that this ligand/receptor pair has a specific role in controlling myeloid cell function. In addition to CD200R, several related genes have been identified. Whether these gene products also regulate immune function is controversial. CD200R is also expressed by certain subsets of T cells and CD200 may be expressed by antigen-presenting cells, adding additional layers of complexity to the CD200/CD200R axis. Because monocytic myeloid cells provide a link between the innate and adaptive immune response, mechanisms to control their function through receptors such as CD200R will have therapeutic potential. Regulation of immune responses is accomplished by the concerted, but opposing, activity of kinases and phosphatases, fine control often being achieved through paired receptors. In this review, we will consider whether CD200R signaling functions within a framework of paired activating and inhibitory receptors and whether the inhibitory signal delivered has functional consequences beyond inhibition of myeloid cell proinflammatory activation.