Disease relevance of Cd200

• Onset and severity of uveitogenic peptide (1-20) of interphotoreceptor retinoid-binding protein-induced experimental autoimmune uveoretinitis is accelerated in CD200(-/-) mice and although tissue destruction appears no greater than seen in CD200(+/+) mice, there is continued increased ganglion and photoreceptor cell apoptosis [1].
• Despite earlier onset of experimental autoimmune uveitis in sham-tolerized, CD200-deficient mice, disease incidence and subsequent severity were actually reduced compared with those in wild-type mice [2].
• Halting disease progression and tolerance in CD200(-/-) mice correlated with a marked increase in Th2-associated cytokine production by Ag-challenged splenocytes [2].
• Because manipulation of the CD200-CD200R interaction affects the outcome of rodent disease models, targeting of this pathway may have therapeutic utility [3].
• Double-immunofluorescence staining of cerebellar interneurone cultures with MRC OX-2 antibody and tetanus toxin showed that all tetanus-positive cells (neurones) were MRC OX-2-positive [4].

High impact information on Cd200

• Down-regulation of the macrophage lineage through interaction with OX2 (CD200) [5].
• Upon facial nerve transection, damaged CD200-deficient neurons elicited an accelerated microglial response [5].
• Putting the brakes on innate immunity: a regulatory role for CD200 [6]?
• In all, we provide direct evidence that the CD200-CD200R interaction controls monocyte/macrophage function in both murine and human systems, further supporting the potential clinical application of CD200R agonists for the treatment of chronic inflammatory diseases [7].
• Enhanced tolerance to autoimmune uveitis in CD200-deficient mice correlates with a pronounced Th2 switch in response to antigen challenge [2].

Biological context of Cd200

• In CD200(-/-) mice the release of suppression of tonic macrophage activation, supported by increased NOS2 expression in the CD200(-/-) steady state accelerates disease onset but without any demonstration of increased target organ/tissue destruction [1].
• Thus, mice lacking CD200 (CD200(-/-)) show increased susceptibility to and accelerated onset of tissue-specific autoimmunity [1].
• Collectively, these results suggest that the expression of CD200 in follicular epithelium attenuates inflammatory reactions and may play a role in maintaining immune tolerance to HF-associated autoantigens [8].
• We now report that freshly isolated cells of the murine epidermis contain a subpopulation of major histocompatibility complex (MHC) class II-negative, CD3-negative keratinocytes that are CD200-positive [8].
• Blocking MD-1 gene expression inhibits surface expression of CD80 and CD86, but not of OX2 [9].

Anatomical context of Cd200

• Myeloid cell infiltrate was increased in CD200(-/-) mice during experimental autoimmune uveoretinitis, although NOS2 expression was not heightened [1].
• Constitutive retinal CD200 expression regulates resident microglia and activation state of inflammatory cells during experimental autoimmune uveoretinitis [1].
• In the retina there is extensive expression of CD200 on neurons and retinal vascular endothelium [1].
• There was a 2-fold increase in graft-infiltrating T cells in CD200-deficient skin at 14 d [8].
• Expression of CD200 on epithelial cells of the murine hair follicle: a role in tissue-specific immune tolerance [8]?

Associations of Cd200 with chemical compounds

• CD200 (OX2) is a membrane glycoprotein that interacts with a structurally related receptor (CD200R) involved in the regulation of macrophage function [10].
• The purified brain and thymocyte OX 2 antigens were glycoproteins with apparent Mr 41000 and 47000 respectively as determined by polyacrylamide gel electrophoresis in sodium dodecyl sulphate [11].
• Both OX 2 antigens contained carbohydrate residues typical of structures N-linked to asparagine but lacked galactosamine, indicating the absence of O-linked structures [11].
• Thymocyte OX 2 contained higher levels of galactose and sialic acid but less fucose than brain OX 2 [11].
• The OX 2 antigens recognised by this antibody were purified from brain and thymus, by solubilisation with sodium deoxycholate, affinity chromatography with MRC OX 2 antibody and gel filtration [11].

Regulatory relationships of Cd200

• Alopecia and skin lesions were induced in CD200-deficient hosts by adoptive transfer of splenocytes from WT mice previously grafted with CD200-negative skin, but not from mice grafted with WT skin [8].
• CD 200 is a widely expressed transmembrane glycoprotein that transmits an inhibitory signal after ligation of the structurally homologous CD 200-receptor-1 (CD 200 R1) [12].

Other interactions of Cd200

• When syngeneic skin grafts were exchanged between gender-matched wild-type (WT) and CD200-deficient C57BL/6 mice, significant perifollicular and intrafollicular inflammation was observed, eventually leading to the destruction of virtually all HF (alopecia) without significant loss of the CD200-negative grafts [8].
• Engagement of CD200R by CD200 inhibits activation of myeloid cells [13].
• Increased expression of OX2 on dendritic cells (DC) in vivo following preimmunization via the portal vein is also associated with elevated expression of MD-1 [9].
• The immunoadhesin (OX2:Fc) comprising the extracellular domain of murine OX2 linked to IgG2aFc, inhibits production of IL-2 and IFN-gamma by activated T cells and increases allograft and xenograft survival in vivo [9].
• BACKGROUND: CD200 is a transmembrane protein delivering immunoregulatory signals after engagement of CD200R [14].

Analytical, diagnostic and therapeutic context of Cd200

• The CD200-COMP gave strong signals in protein microarrays, suggesting that such reagents may be valuable in high throughput detection of weak interactions [10].
• The epitope for the MRC OX2 mAb and a site for ligand binding were mapped to domain 1 by site-directed mutagenesis [15].
• RESULTS: Only mAbs defining epitopes in the N-terminal domain could augment MLC reactivity (or block immunosuppression by soluble CD200Fc), whereas mAbs targeting C-domain epitopes, although reactive in ELISA or FACS (targeting cell surface CD200), were inactive in MLCs [16].
• CD200 immunoadhesin suppresses collagen-induced arthritis in mice [17].
• In vitro studies with an OX2:Fc immunoadhesion had suggested that immunosuppression induced by this soluble form of the OX2 molecule was dependent primarily upon an early (OX2-dependent) signal [18].

References