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

Transplantation. 2007 Jul 27;84(2):251-7. doi: 10.1097/01.tp.0000269795.04592.cc.

Abstract

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 CD200R1+ stimulatory cells, although maximal immunoregulation by CD200Fc occurred only when CD200R1+ T responder cells also were used. CD200Fc failed to suppress graft rejection in CD200R1(-/-) mice.

Conclusion: CD200:CD200R1 plays an immunoregulatory role in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Surface* / genetics
  • Antigens, Surface* / immunology
  • Blotting, Southern
  • Cells, Cultured
  • Disease Models, Animal
  • Female
  • Flow Cytometry
  • Gene Expression*
  • Graft Rejection / immunology
  • Graft Rejection / metabolism*
  • Graft Rejection / pathology
  • Graft Survival
  • Lipopolysaccharides / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myeloid Cells / metabolism
  • Myeloid Cells / pathology
  • Orexin Receptors
  • RNA, Messenger / genetics*
  • Receptors, Cell Surface* / deficiency
  • Receptors, Cell Surface* / genetics
  • Receptors, Cell Surface* / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin Transplantation / immunology*
  • Spleen / metabolism
  • Spleen / pathology
  • Transplantation, Homologous
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / drug effects

Substances

  • Antigens, Surface
  • Cd200r1 protein, mouse
  • Lipopolysaccharides
  • Orexin Receptors
  • RNA, Messenger
  • Receptors, Cell Surface
  • Tumor Necrosis Factor-alpha