CD200/CD200R在异基因造血干细胞移植后的表达水平及意义
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摘要
背景和目的
CD200与其受体CD200R均为跨膜糖蛋白,均属于免疫球蛋白超家族的成员,CD200在体内存在广泛。CD200与CD200R的相互作用对于免疫调节的影响已经在动物以及体外实验中得到了证实,除了对巨噬细胞具有抑制作用以外,有研究表明,在调节性T细胞的调节、过敏反应、自体免疫、同种异体移植、神经系统疾病以及其他一些自身免疫性疾病中,CD200/CD200R均发挥着重要的作用。CD200在急性白血病、多发性骨髓瘤及慢性淋巴细胞白血病等恶性疾病中高表达,且与预后相关,因此可将CD200作为这些疾病的预后因素.CD200/CD200R与异基因造血干细胞移植之间的关系鲜有报道,因此本文主要对CD200及其受体在移植物抗宿主病(graft versus host disease, GVHD)中的作用进行探讨。
研究方法
实验标本来源于2013年2月至2013年12月在北京协和医院就诊的异基因造血干细胞移植患者。首先应用流式细胞术测定各研究组患者细胞表面CD200及CD200R在CD19+细胞、CD3+细胞及树突状细胞(CD19-CD14-CD1c+)表面表达水平的差异。随后通过应用实时荧光定量聚合酶链反应技术在mRNA水平对各研究组CD200及CD200R的表达量进行检测,观察各组间mRNA表达水平的差异。最后将各研究组外周血单个核细胞与抗-CD200R1抗体体外共培养48h,采用酶联免疫吸附剂测定法测定培养上清的白介素-10水平,间接验证CD200/CD200R的功能。
研究结果
1、aGVHD组和non-aGVHD组CD19+CD200+细胞的表达水平低于正常对照组。non-aGVHD组CD19+CD200+细胞的表达水平高于aGVHD组(P<0.05)。
2、 cGVHD组CD19+CD200+细胞的表达水平与正常对照组无差异,non-cGVHD组CD19+CD200+细胞的表达水平高于正常对照组。non-cGVHD组CD19+CD200+细胞的表达水平高于cGVHD组。(P<0.05)
3、CD3+细胞和树突状细胞CD200及CD200R的表达在各研究组间无差异。
4、 aGVHD组和cGVHD组CD200的mRNA表达水平均低于正常对照组(P<0.05)。
5、 aGVHD组CD200的mRNA表达水平低于non-aGVHD组,cGVHD组低于non-cGVHD组(P<0.05)。
6、 non-aGVHD组患者CD200的mRNA的表达水平与正常对照组无差异,non-cGVHD组高于正常对照组(P<0.05)。
7、CD200R的mRNA的表达水平在各研究组间未见明显差异。
8、抗-CD200R1抗体与各实验组外周血单个核细胞体外共培养48h后,细胞上清IL-10浓度随抗-CD200R1抗体浓度的增加呈下降趋势。
结论
研究显示,发生GVHD的患者CD200的]mRNA表达水平明显低于同时间点未发生GVHD患者及正常对照组。aGVHD组患者CD19+CD200+细胞表达水平低于non-aGVHD组,cGVHD组低于non-cGVHD组。提示CD200与GVHD的发生可能有一定的相关性,CD19+CD200+细胞在GVHD的致病机制中发挥着一定的作用。
Background and Objective
CD200and its receptor CD200R are both type-1membrane glycoproteins, which are members of the immunoglobulin superfamily (IgSF). CD200is widely expressed on a variety of cell types, while the recently identified CD200R is expressed on myeloid cells and T cells. The immunomodulatory effects of CD200and CD200R interactions have been demonstrated in animal models and in vitro experiments. Besides the inhibition effects on macrophages, CD200/CD200R also play an important role in regulating the regulatory T cells, allergicreaction, autoimmune diseases, allograft, neurological diseases and other autoimmune-related diseases, etc. CD200is highly expressed in patients with acute leukemia, multiple myeloma, chronic lymphocytic leukemia and other malignant diseases. CD200is considered to be associated with the prognosis of these diseases, and it could be used as an independent prognostic factor. The relationship between CD200/CD200R and allogeneic hematopoietic stem cell transplantation has been reported rarely. Therefore, this paper mainly focuses on the role of CD200and its receptor in the graft versus host disease (GVHD).
Methods
Experimental samples were collected from the allogeneic hematopoietic stem cell transplantation patients who were treated in Peking Union Medical College Hospital from February2013to December2013. Firstly, the expression levels of CD200and CD200R on CD19+cell, CD3+cell and dendritic cell (CD19-CD14-CDlc+) surface in each research group were detected by using flow cytometry, to determine whether there were expression differences among each group. Then, the mRNA levels of each research group were tested by using real-time quantitative polymerase chain reaction, to find the differences of mRNA expression levels among each group. Finally, the peripheral blood mononuclear cells of the patients and healthy controls were co-cultured with anti-CD200R1antibody for48hours, and the interleukin-10levels in the co-culture system were tested by using enzyme linked immunosorbent assay, to indirectly verify the function of CD200/CD200R.
Results
1、 The CD200expression levels on CD19+cells surface in the aGVHD group and non-aGVHD group were both lower than healthy control group.The CD200expression levels on CD19+cells surface in the non-aGVHD group were higher than the aGVHD group(P<0.05).
2、There was no significant difference of the expression levels of CD19+CD200+cells between the cGVHD group and healthy control group. The expression levels of CD19+CD200+cells in the non-cGVHD group were higher than the cGVHD group and healthy control group(P<0.05).
3、 There were no significant differences of CD200and CD200R expression levels on CD3+cells and dendritic cells among all research groups.
4、 The CD200mRNA expression levels in the aGVHD group and cGVHD group were both lower than the healthy control group(P<0.05).
5、 The CD200mRNA expression levels were lower in the aGVHD group than the non-aGVHD group, and were lower in the cGVHD group than the non-cGVHD group(P <0.05).
6、 The CD200mRNA expression levels had no significant difference between the non-aGVHD patients and the healthy control group, but were higher in the non-cGVHD group than the healthy control group (P<0.05).
7、There was no significant difference of the CD200R mRNA expression levels among all research groups.
8、 After the peripheral blood mononuclear cells of the patients and healthy controls were co-cultured with anti-CD200R1antibody for48hours, the interleukin-10concentration decreased with the increasing concentrations of anti-CD200R1antibody in the co-culture system.
Conclusion
The study showed that the patients with GVHD had a significantly lower CD200mRNA levels than the patients without GVHD and the healthy control group. The CD200expression levels of CD19+cells in the patients with aGVHD were also lower than the non-aGVHD group. These results indicate that CD200and CD19+CD200+cells play a role in the pathogenesis of GVHD.
CD200与其受体CD200R均为跨膜糖蛋白,均属于免疫球蛋白超家族的成员,CD200在体内存在广泛。CD200与CD200R的相互作用对于免疫调节的影响已经在动物以及体外实验中得到了证实,除了对巨噬细胞具有抑制作用以外,有研究表明,在调节性T细胞的调节、过敏反应、自体免疫、同种异体移植、神经系统疾病以及其他一些自身免疫性疾病中,CD200/CD200R均发挥着重要的作用。CD200在急性白血病、多发性骨髓瘤及慢性淋巴细胞白血病等恶性疾病中高表达,且与预后相关,因此可将CD200作为这些疾病的预后因素.CD200/CD200R与异基因造血干细胞移植之间的关系鲜有报道,因此本文主要对CD200及其受体在移植物抗宿主病(graft versus host disease, GVHD)中的作用进行探讨。
研究方法
实验标本来源于2013年2月至2013年12月在北京协和医院就诊的异基因造血干细胞移植患者。首先应用流式细胞术测定各研究组患者细胞表面CD200及CD200R在CD19+细胞、CD3+细胞及树突状细胞(CD19-CD14-CD1c+)表面表达水平的差异。随后通过应用实时荧光定量聚合酶链反应技术在mRNA水平对各研究组CD200及CD200R的表达量进行检测,观察各组间mRNA表达水平的差异。最后将各研究组外周血单个核细胞与抗-CD200R1抗体体外共培养48h,采用酶联免疫吸附剂测定法测定培养上清的白介素-10水平,间接验证CD200/CD200R的功能。
研究结果
1、aGVHD组和non-aGVHD组CD19+CD200+细胞的表达水平低于正常对照组。non-aGVHD组CD19+CD200+细胞的表达水平高于aGVHD组(P<0.05)。
2、 cGVHD组CD19+CD200+细胞的表达水平与正常对照组无差异,non-cGVHD组CD19+CD200+细胞的表达水平高于正常对照组。non-cGVHD组CD19+CD200+细胞的表达水平高于cGVHD组。(P<0.05)
3、CD3+细胞和树突状细胞CD200及CD200R的表达在各研究组间无差异。
4、 aGVHD组和cGVHD组CD200的mRNA表达水平均低于正常对照组(P<0.05)。
5、 aGVHD组CD200的mRNA表达水平低于non-aGVHD组,cGVHD组低于non-cGVHD组(P<0.05)。
6、 non-aGVHD组患者CD200的mRNA的表达水平与正常对照组无差异,non-cGVHD组高于正常对照组(P<0.05)。
7、CD200R的mRNA的表达水平在各研究组间未见明显差异。
8、抗-CD200R1抗体与各实验组外周血单个核细胞体外共培养48h后,细胞上清IL-10浓度随抗-CD200R1抗体浓度的增加呈下降趋势。
结论
研究显示,发生GVHD的患者CD200的]mRNA表达水平明显低于同时间点未发生GVHD患者及正常对照组。aGVHD组患者CD19+CD200+细胞表达水平低于non-aGVHD组,cGVHD组低于non-cGVHD组。提示CD200与GVHD的发生可能有一定的相关性,CD19+CD200+细胞在GVHD的致病机制中发挥着一定的作用。
Background and Objective
CD200and its receptor CD200R are both type-1membrane glycoproteins, which are members of the immunoglobulin superfamily (IgSF). CD200is widely expressed on a variety of cell types, while the recently identified CD200R is expressed on myeloid cells and T cells. The immunomodulatory effects of CD200and CD200R interactions have been demonstrated in animal models and in vitro experiments. Besides the inhibition effects on macrophages, CD200/CD200R also play an important role in regulating the regulatory T cells, allergicreaction, autoimmune diseases, allograft, neurological diseases and other autoimmune-related diseases, etc. CD200is highly expressed in patients with acute leukemia, multiple myeloma, chronic lymphocytic leukemia and other malignant diseases. CD200is considered to be associated with the prognosis of these diseases, and it could be used as an independent prognostic factor. The relationship between CD200/CD200R and allogeneic hematopoietic stem cell transplantation has been reported rarely. Therefore, this paper mainly focuses on the role of CD200and its receptor in the graft versus host disease (GVHD).
Methods
Experimental samples were collected from the allogeneic hematopoietic stem cell transplantation patients who were treated in Peking Union Medical College Hospital from February2013to December2013. Firstly, the expression levels of CD200and CD200R on CD19+cell, CD3+cell and dendritic cell (CD19-CD14-CDlc+) surface in each research group were detected by using flow cytometry, to determine whether there were expression differences among each group. Then, the mRNA levels of each research group were tested by using real-time quantitative polymerase chain reaction, to find the differences of mRNA expression levels among each group. Finally, the peripheral blood mononuclear cells of the patients and healthy controls were co-cultured with anti-CD200R1antibody for48hours, and the interleukin-10levels in the co-culture system were tested by using enzyme linked immunosorbent assay, to indirectly verify the function of CD200/CD200R.
Results
1、 The CD200expression levels on CD19+cells surface in the aGVHD group and non-aGVHD group were both lower than healthy control group.The CD200expression levels on CD19+cells surface in the non-aGVHD group were higher than the aGVHD group(P<0.05).
2、There was no significant difference of the expression levels of CD19+CD200+cells between the cGVHD group and healthy control group. The expression levels of CD19+CD200+cells in the non-cGVHD group were higher than the cGVHD group and healthy control group(P<0.05).
3、 There were no significant differences of CD200and CD200R expression levels on CD3+cells and dendritic cells among all research groups.
4、 The CD200mRNA expression levels in the aGVHD group and cGVHD group were both lower than the healthy control group(P<0.05).
5、 The CD200mRNA expression levels were lower in the aGVHD group than the non-aGVHD group, and were lower in the cGVHD group than the non-cGVHD group(P <0.05).
6、 The CD200mRNA expression levels had no significant difference between the non-aGVHD patients and the healthy control group, but were higher in the non-cGVHD group than the healthy control group (P<0.05).
7、There was no significant difference of the CD200R mRNA expression levels among all research groups.
8、 After the peripheral blood mononuclear cells of the patients and healthy controls were co-cultured with anti-CD200R1antibody for48hours, the interleukin-10concentration decreased with the increasing concentrations of anti-CD200R1antibody in the co-culture system.
Conclusion
The study showed that the patients with GVHD had a significantly lower CD200mRNA levels than the patients without GVHD and the healthy control group. The CD200expression levels of CD19+cells in the patients with aGVHD were also lower than the non-aGVHD group. These results indicate that CD200and CD19+CD200+cells play a role in the pathogenesis of GVHD.
引文
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[31]Stumpfova M, Ratner D, Desciak EB, Eliezri YD, Owens DM. The immunosuppressive surface ligand CD200 augments the metastatic capacity of squamous cell carcinoma [J]. Cancer Res,2010,70(7):2962-72.
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[44]Matsue H. CD 200-mediated regulation of skin immunity [J]. J Invest Dermatol, 2005,125(6):2691-2698.
[45]Garza La, Yang CC, Zhao T, et al. Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells [J]. J Clin Invest,2011,121(2):613-622.
[46]Rosenblum MD, Yancey KB, Olasz EB, Truitt RL. CD200, a "no danger" signal for hair follicles [J]. J Dermatol Sci,2006,41(3):165-174.
[47]Miyajima I, Dombrowicz D, Martin TR, Ravetch JV, Kinet JP, Galli SJ. Systemic anaphylaxis in the mouse can be mediated largely through iggl and Fc gammaRⅢ. Assessment of the cardiopulmonary changes, mast cell degranulation, and death associated with active or IgE-or IgGl-dependent passive anaphylaxis [J]. J Clin Invest, 1997,99(5):901-914.
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[50]Matsumoto H, Kumon Y, Watanabe H, et al. Expression of CD200 by macrophage-like cells in ischemic core of rat brain after transient middle cerebral artery occlusion [J]. Neurosci Lett,2007,418(1):44-48.
[51]Walker DG, Dalsing-Hernandez JE, Campbell NA, Lue LF. Decreased expression of CD200 and CD200 receptor in Alzheimer's disease:a potential mechanism leading to chronic inflammation [J]. Exp Neurol,2009,215(1):5-19.
[52]Frank MG, Barrientos RM, Biedenkapp JC, et al. mRNA up-regulation of MHC II and pivotal pro-inflammatory genes in normal brain aging [J]. Neurobiol Aging, 2006,27(5):717-722.
[53]Wang XJ, Ye M, Zhang YH, Chen SD. CD200/CD200R regulation of microglia activation in the pathogenesis of Parkinson's disease [J]. J Neuroimmune Pharmacol, 2007,2(3):259-264.
[54]Hoek RM, Ruuls SR, Murphy CA, et al. Down-regulation of macrophage lineage through interaction with OX2(CD200) [J]. Science,2000,290(5497):1768-1771.
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[1]McMaster WR, Williams AF. Identification of la glycoproteins in rat thymus and purification from rat spleen [J]. Eur J Immunol,1979,9(6):426-33.
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[4]Zhang S, Cherwinski H, Sedgwick JD, Phillips JH. Molecular mechanisms of CD200 inhibition of mast cell activation [J]. J Immunol,2004,173:6786-6793.
[5]Gorczynshi RM, Yu K, Clark D. Receptor engagement on cells expressing a ligand for the tolerance-inducing molecule OX2 induces an immunoregulatory population that inhibits alloreactivity in vitro and in vivo [J]. J Immunol,2000,165(9):4854-4860.
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[9]Mihrshahi R, Barclay AN, Brown MH. Essential roles for DOK2 and RasGAP in CD200 receptor-mediated regulation of human myeloid cells [J]. J Immunol, 2009,183(8):4879-86.
[10]Zhang S, Cherwinski H, Sedgwick JD, et al. Molecular mechanisms of CD200 inhibition of mast cell activation [J]. J Immunol,2004,173(11):6786-93.
[11]Shurin MR, Lu L, Kalinski P, et al. Thl/Th2 balance in cancer, transplantation and pregnancy [J]. Springer Semin Immunopathol.1999,21(3):339-359.
[12]Gorczynshi RM, Chen Z, Fu XM, et al. Increased expression of the novel molecule OX-2 is involved in prolongation of murine renal allograft survival [J]. Transplantation, 1998,65(8):1106-1114.
[13]Gorczynshi RM, Cattral MS, Chen Z, et al. An immunoadhesin incorporating the molecule OX-2 is a potent immunosuppressant that prolong allo-and xenograft survival [J]. J Immunol,1999,163(3):1654-1660.
[14]Gorczynshi RM. Transplant tolerance modifying antibody to CD200 receptor, but not CD200, alters cytokine production profile from stimulated macrophage [J]. Eur J Immunol,2011,31(8):2331-2337.
[15]Gorczynski RM, Chen Z, He w, Khatri I, Sun Y, Yu K, Boudakov I. Expression of a CD200 transgene is necessary for induction but not maintenance of tolerance to cardiac and skin allografts [J]. J immunol,2009,183(3):1560-1568.
[16]Gorczynski R, Chen Z, Shivagnahnam S, Taseva A, Wong K, Yu K, Khatri I. CD200Fc(gly)6TGFβ suppresses transplant rejection and MLCs in vitro [J]. J Immunol 2010,184,49.15.
[17]Gorczynski R, Chen Z, Shivagnahnam s, Taseva a, Wong K, Yu K, Khatri I. Potent immunosuppression by a bivalent molecule binding to CD200R and TGF-beta [J]. Transplantation 2010,90(2):150-159.
[18]Holt PG, Strickland DH. The CD200-CD200R axis in local control of lung inflammation [J]. Nat Immunol,2008,9(9):1011-1013.
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[24]Moreaux J, Veyrune JL, Reme T, De Vos J, Klein B. CD200:a putative therapeutic target in cancer [J]. Biochem Biophys Res Commun,2008,366(1):117-22.
[25]Tonks A, Hills R, White P, Rosie B, Mills KI, Burnett AK, Darley RL. CD200 as a prognostic factor in acute myeloid leukaemia [J]. Leukemia,2007,21(3):566-568.
[26]Moreaux J, Hose D, Reme T, et al. CD200 is a new prognostic factorr in multiple myeloma [J]. B100d,2006,108(13):4194-4197.
[27]Pallasch CP, Ulbrich S, Brinker R, Hallek M, Uger RA, Wendtner CM. Disruption of T cell suppression in chronic lymphocytic leukemia by CD200 blockade [J]. Leuk Res, 2009; 33(3):460-464.
[28]Dorfman DM, Shahsafaei A. CD200 (OX-2) membrane glycoprotein expression in B cell-derived neoplasms [J]. Am J Clin Pathol,2010,134(5):726-733.
[29]Kawasaki BT, Mistree T, Hurt EM, Kalathur M, Farrar WL. Co-expression of the tolerogenic glycoprotein CD200, with markers for cancer stem cells [J]. Biochem Biophys Res Commun,2007,364(4):778-782.
[30]Gorczynski RM, Clark DA, Erin N, Khatri I Breast cancer cells CD200 expression regulates immune response to EMT6 tumor cells in mice [J]. Breast Cancer Res Treat, 2010,123(2):405-415.
[31]Stumpfova M, Ratner D, Desciak EB, Eliezri YD, Owens DM. The immunosuppressive surface ligand CD200 augments the metastatic capacity of squamous cell carcinoma [J]. Cancer Res,2010,70(7):2962-72.
[32]Krejsek J, Kolackova M, Mandak J, et al. Expression of CD200/CD200R regulatory molecules on granulocytes and monocytes is modulated by cardiac surgical operation [J]. Perfusion,2010,25(6):389-397.
[33]Curiel TJ, Coukos G, Zou L, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival [J]. Nat Med, 2004,10(9):942-949.
[34]Gorczynski RM, Lee L, Boudakov I. Augmented induction of CD4+CD25+Treg using monoclonal antibodies to CD200R [J]. Transplantation,2005,79(4):488-491.
[35]Gorczynski R, Khatri I, Lee L, et al. An interaction between CD200 and monoclonal antibody agonists to CD200R2 in development of dendritic cells that preferentially induce populations of CD4+CD25+T regulatory cells [J]. J Immunol,2008, 180(9):5946-5955.
[36]Lin H, Mosmann TR, Guilbert L, et al. Synthesis of T helper 2-type cytokines at the maternal-fetal interface [J]. J Immunol,1993,151(9):4562-4573.
[37]Wegmann TG, Lin H, Guilbert L, et al. Bidirectional cytokine interaction in the maternal-fetal relationship:is successful pregnancy a TH2 phenomenon? [J]. Immunol Today,1993,14(7):353-356.
[38]Clark DA, Keil A, Chen Z, et al. Placental trophoblast from successful human pregnancies expresses the tolerance signaling molecule, CD200(OX-2) [J]. Am J Reprod Immunol,2003,50(3):187-195.
[39]Chung YH, Means RE, Choi JK,Lee BS, Jung JU. Kaposi's sarcoma-associated herpesvirus OX2 glycoprotein activates myeloid-lineage cells to induce inflammatory cytokine production [J]. J virol,2002,76(10):4688-4698.
[40]Yu G, Sun Y, Foerster K, Manuel J, et al. LPS-induced murine abortions require C5 but not C3, and are prevented by upregulating expression of the CD200 tolerance signaling molecule [J]. Am J Reprod immunol 2008,60(2):135-140.
[41]Ko YC, Chien HF, Jiang-Shieh YF, et al. Endothelial CD200 is heterogeneously distributed, regulated and involved in immune cell-endothelium interactions [J]. J Anat, 2009,214(1):183-195.
[42]Krejsek J, Kolackova M, Mandak J, et al. Expression of CD200/CD200R regulatory molecules on granulocytes and monocytes is modulated by cardiac surgical operation [J]. Perfusion,2010,25(6):389-397.
[43]Rubino AS, Serraino GF, Mariscalco G, Marsico R, Sala A, Renzulli A. Leukocyte depletion during extracorporeal circulation allows better organ protection but does not change hospital outcomes [J]. Ann Thorac Surg,2011,91:534-540.
[44]Matsue H. CD 200-mediated regulation of skin immunity [J]. J Invest Dermatol, 2005,125(6):2691-2698.
[45]Garza La, Yang CC, Zhao T, et al. Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells [J]. J Clin Invest,2011,121(2):613-622.
[46]Rosenblum MD, Yancey KB, Olasz EB, Truitt RL. CD200, a "no danger" signal for hair follicles [J]. J Dermatol Sci,2006,41(3):165-174.
[47]Miyajima I, Dombrowicz D, Martin TR, Ravetch JV, Kinet JP, Galli SJ. Systemic anaphylaxis in the mouse can be mediated largely through iggl and Fc gammaRⅢ. Assessment of the cardiopulmonary changes, mast cell degranulation, and death associated with active or IgE-or IgGl-dependent passive anaphylaxis [J]. J Clin Invest, 1997,99(5):901-914.
[48]Cherwinski HM, Murphy CA, Joyce BL, et al. The CD200 receptor is a novel and potent regulator of murine and human mast cell function [J]. J Immunol,2005,174(3): 1348-1356.
[49]Zhang S, Cherwinski H, Sedgwick JD, Phillips JH. Molecular mechanisms of CD200 inhibition of mast cell activation [J]. J Immunol,2004,173(11):6786-6793.
[50]Matsumoto H, Kumon Y, Watanabe H, et al. Expression of CD200 by macrophage-like cells in ischemic core of rat brain after transient middle cerebral artery occlusion [J]. Neurosci Lett,2007,418(1):44-48.
[51]Walker DG, Dalsing-Hernandez JE, Campbell NA, Lue LF. Decreased expression of CD200 and CD200 receptor in Alzheimer's disease:a potential mechanism leading to chronic inflammation [J]. Exp Neurol,2009,215(1):5-19.
[52]Frank MG, Barrientos RM, Biedenkapp JC, et al. mRNA up-regulation of MHC II and pivotal pro-inflammatory genes in normal brain aging [J]. Neurobiol Aging, 2006,27(5):717-722.
[53]Wang XJ, Ye M, Zhang YH, Chen SD. CD200/CD200R regulation of microglia activation in the pathogenesis of Parkinson's disease [J]. J Neuroimmune Pharmacol, 2007,2(3):259-264.
[54]Hoek RM, Ruuls SR, Murphy CA, et al. Down-regulation of macrophage lineage through interaction with OX2(CD200) [J]. Science,2000,290(5497):1768-1771.
[55]Boudakov I, Liu J, Fan N, Gulay P, et al. Mice lacking CD200R1 show absence of suppression of lipopolysaccharide-induced tumor necrosis factor-alpha and mixed leukocyte culture responses by CD200 [J]. Transplantation,2007,84(2):251-257.
[56]Chitnis T, Imitola J, Wang Y, et al. Elevated neuronal expression of CD200 protects Wlds mice from inflammation-mediated neurodegeneration [J]. Am J Pathol,2007, 170(5):1695-1712.
[57]Banerjee D, Dick AD. Blocking CD200-CD200 receptor axis augments NOS-2 expression and aggravates experimental autoimmune uveoretinitis in Lewis rats [J]. Ocul Immunol Inflammm,2004,12(2):115-125.
[58]Copland DA, Calder CJ, Raveney BJ, et al. Monoclonal antibody-mediated CD200 receptor signaling suppresses macrophage activation and tissue damage in experimental autoimmune uveoretinitis [J]. Am J Pathol,2007,171(2):580-588.