Mice lacking CD200R1 show absence of suppression of lipopolysaccharide-induced tumor necrosis factor-α and mixed leukocyte culture responses by CD200

Background. CD200:CD200R interactions deliver immunoregulatory signals. A family of CD200Rs (CD200R1-5) has been described, and engagement of CD200R1 by its ligand CD200 suppresses LPS-induced macrophage cytokine production, decreases alloimmune responses in vivo and in vitro, and suppresses collagen-induced arthritis. Methods. We generated C57BL/6 mice lacking the genomic exons encoding the extracellular domains of the CD200R1 molecule using transformation of ES cells and explored cell subtypes and immune responses in these mice. Results. Myeloid cells/splenocytes from CD200R1(-/-) mice were not stained in FACS by anti-CD200R1 mAb. Stimulation of splenic tumor necrosis factor-alpha production by lipopolysaccharide was enhanced relative to control ((+/+)) mice and was not suppressed by addition of exogenous CD200Fc. Modulation of alloreactivity in mixed leukocyte cultures by CD200Fc depended upon CD200RI(+) stimulatory cells, although maximal immunoregulation by CD200Fc occurred only when CD200RI(+) T responder cells also were used. CD200Fc failed to suppress graft rejection in CD200R1(-/-) mice. Conclusion. CD200:CD200R1 plays an immunoregulatory role in vivo.