Mice lacking CD200R1 show absence of suppression of lipopolysaccharide-induced tumor necrosis factor-alpha 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 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.


CONCLUSIONS
CD200:CD200R1 plays an immunoregulatory role in vivo.
University Health Network, Transplant Research Division, MaRS Medical Discovery Tower, Toronto, Ontario, Canada.
Ivo
I
Boudakov
Jian
J
Liu
Na
N
Fan
Pelin
P
Gulay
Karrie
K
Wong
Reg M
RM
Gorczynski
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology; D015139:Blotting, Southern; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006084:Graft Rejection / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006085:Graft Survival; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000378:metabolism / Q000473:pathology; D064446:Orexin Receptors; D012333:RNA, Messenger / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016038:Skin Transplantation / Q000276:immunology*; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects
D000954:Antigens, Surface; C501103:Cd200r1 protein, mouse; D008070:Lipopolysaccharides; D064446:Orexin Receptors; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha