Disease relevance of CD200

• Distant, but recognizable, homologues of CD200 have been identified in many herpesviruses and poxviruses [1].
• Antibodies binding the immunosuppressive molecule CD200 were identified by cell panning of an antibody phage display library derived from rabbits immunized with primary CLL cells [2].
• Down-regulation of basophil function by human CD200 and human herpesvirus-8 CD200 [3].
• Previous studies have shown that CD200 plays an important role in prevention of graft rejection, autoimmune diseases and spontaneous abortion [4].
• Lack of CD200 resulted in a more rapid onset of experimental autoimmune encephalomyelitis (EAE) [5].
• Melanoma cell lines expressing endogenous CD200 repressed primary T cell activation by DCs, while knockdown of CD200 by shRNA abrogated this immunosuppressive effect [6].

Psychiatry related information on CD200

• MRC to open new CJD research unit.. [7].
• Clinical assessment was conducted with the MRC score in 28 muscles and a self-evaluation scale (five daily motor activities scored from 0 to 5) [8].
• Risk factors for Alzheimer's disease and dementia: a case-control study based on the MRC elderly hypertension trial [9].
• In collaboration with several companies and government departments, the MRC Applied Psychology Unit performed a series of auditory warning studies [10].
• METHOD: Measures of anxiety and depression and potential alcohol abuse at age 43 were compared in 2085 participants from the MRC National Survey of Health and Development who were either married and never divorced or separated, or who had divorced or separated at least once [11].

High impact information on CD200

• We also report the results of a project at the MRC UK Mouse Genome Centre targeted at chromosome X. The project produced a YAC-based map containing 619 loci (with 121 loci in common with the Whitehead map and 498 additional loci), providing especially dense coverage of this sex chromosome [12].
• MRC to fund mouse genome centre [13]?
• Human genome. MRC follows NIH on patents [14].
• Spina bifida: MRC folate trials to start at last [15].
• OX2 (CD200) is a broadly expressed membrane glycoprotein, shown here to be important for regulation of the macrophage lineage [5].

Chemical compound and disease context of CD200

• Fludarabine and cytosine are less effective than standard ADE chemotherapy in high-risk acute myeloid leukemia, and addition of G-CSF and ATRA are not beneficial: results of the MRC AML-HR randomized trial [16].
• The MRC AML (Medical Research Council Acute Myeloid Leukemia) Working Group designed a trial comparing fludarabine and high-dose cytosine (FLA) with standard chemotherapy comprising cytosine arabinoside, daunorubicin, and etoposide (ADE) [16].
• Kaposi's sarcoma-associated herpesvirus OX2 glycoprotein activates myeloid-lineage cells to induce inflammatory cytokine production [17].
• A 45-year-old man with a 3-month history of episodic muscle weakness, MRC grade 4/5 symmetric hip flexor weakness, elevated CK, and an inflammatory myopathy was found to have elevated free thyroxine and T3 [18].
• In a double-blind placebo-controlled trial in 24 patients fulfilling the MRC criteria for chronic bronchitis, oral salbutamol 4 mg and slow-release aminophylline (Phyllocontin) 450 mg produced similar and significant (p less than 0.05) mean increases in forced expiratory volume in one second (FEV1) [19].

Biological context of CD200

• The mutagenesis showed that the binding involved the predicted GFCC' face of its N-terminal domain, like that of CD200, suggesting that the interaction evolved from a homotypic interaction [20].
• Several showed decreased binding to the blocking mAb DX136 and OX108, suggesting close proximity of these epitopes to the CD200 binding site [21].
• Antibodies to CD200 prevented downregulation of the Th1 response in most B cell CLL samples evaluated, indicating abrogation of the CD200/CD200R interaction can be sufficient to restore the Th1 response [2].
• B cells from 87 CLL patients exhibited 1.6- to 5.4-fold cell-surface up-regulation of CD200 relative to normal B cells [2].
• METHODS: A transgenic mouse on a C57BL/6 background, expressing a murine CD200 cDNA genetically linked to a green fluorescent protein tag (GFP) under control of a tetracycline response element (TRE), was mated with a commercial transgenic mouse carrying the reverse tetracycline regulated transactivator gene under control of a human CMV promoter [22].

Anatomical context of CD200

• Is the CD200/CD200 receptor interaction more than just a myeloid cell inhibitory signal [23]?
• Both CD200 and CD200R contain two Ig superfamily domains like many other leukocyte membrane proteins [20].
• An effect of increased CD200 expression by CLL cells on the immune system was evaluated in mixed lymphocyte reactions [2].
• CD200 is a type I membrane glycoprotein which is expressed on a number of cell types uniquely relevant to the inflammatory and immune cascade; included in those are dendritic cells, endothelial cells and activated T cells [4].
• In mice lacking CD200, macrophage lineage cells, including brain microglia, exhibited an activated phenotype and were more numerous [5].

Associations of CD200 with chemical compounds

• 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 [23].
• Bilateral orchiectomy, performed 1 week before initiation of weekly sc injections of N-nitrosobis(2-oxopropyl)amine (BOP), prevented induction of hyperplastic and neoplastic lesions in the nasal and paranasal cavities of outbred Wistar-derived MRC rats [24].
• Cross-trial analysis suggests that M7 is comparable to melphalan and prednisone or melphalan, prednisone, and vincristine; that the efficacy of ABCM in the Vth trial and VIth MRC trials is comparable; and that ABCM gave better survival than intermittent melphalan regimens in the prognostic groups analysed [25].
• Regular inhaled salbutamol and asthma control: the TRUST randomised trial. Therapy Working Group of the National Asthma Task Force and the MRC General Practice Research Framework [26].
• Presenting white blood cell count and kinetics of molecular remission predict prognosis in acute promyelocytic leukemia treated with all-trans retinoic acid: result of the Randomized MRC Trial [27].

Physical interactions of CD200

• We report the first characterization of human CD200R (hCD200R) and define its binding characteristics to hCD200 [28].

Regulatory relationships of CD200

• CONCLUSIONS: We conclude that CD200 triggering of bone-marrow DCs in the absence of CD200R1 engagement induces CD4(+)CD25(+) Treg, and these cloned antigen-specific Treg may have clinical utility [29].

Other interactions of CD200

• Site-directed mutagenesis of CD200R showed that, like CD200, it interacted through its N-terminal domain [20].
• Given the high expression of neuronal CD200, which can induce down regulation of CD200 receptor-positive MG activation and neuronal fractalkine expression potentially stimulating MG migration, we wished to further examine their respective roles in the maintenance of MG activation and migration [30].
• In particular, CD34, which delineates hair follicle stem cells in the mouse, is not expressed by human hair follicle stem cells, while CD200 is expressed by stem cells in both species [31].
• Furthermore, IL-10 and CD200 mRNA, molecules that down-regulate macrophage activation, was decreased in older animals [32].
• METHODS: Bone marrow DCp (C3H or BL/6 origin) were cultured for 8 days with GMCSF, IL-4 and anti-CD200R2, or with CD200Fc and a previously described peptide inhibitor of CD200R1 to allow preferential engagement of non-CD200R1 receptors by CD200 [29].

Analytical, diagnostic and therapeutic context of CD200

• METHODS: We used a panel of mAbs to mouse and human CD200Fc to compare the rank activities of antibodies for binding (flow cytometric analysis [FACS] or enzyme-linked immunoadsorbent assay [ELISA]) to CD200 with their abilities to augment immune reactivity in MLCs [33].
• In order to establish protein array technology for the characterization of the weak interactions between leukocyte membrane proteins, we selected the human leukocyte membrane protein CD200 (OX2) and its cell surface receptor (hCD200R) as a model system [21].
• BACKGROUND: CD200 delivers an immunsuppressive signal that augments allograft survival following interaction with its receptor, CD200R1 [22].
• Discrete monoclonal antibodies define functionally important epitopes in the CD200 molecule responsible for immunosuppression function [33].
• Outside the brain, disruption of CD200-CD200 receptor interaction precipitated susceptibility to collagen-induced arthritis (CIA) in mice normally resistant to this disease [5].

References