CD200 immunoadhesin suppresses collagen-induced arthritis in mice

CD200 immunoadhesin suppresses collagen-induced arthritis in mice
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DOI:
10.1006/clim.2001.5117
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发表时间:
2001-12-01
影响因子:
8.6
通讯作者:
Hu, J
Hu, J
中科院分区:
医学3区
文献类型:
--
作者:
Gorczynski, RM;Chen, ZQ;Hu, J

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用弗氏佐剂乳化的100杯牛II型胶原蛋白免疫DBA/1小鼠,18天后在不完全佐剂中加强免疫,注射后数天发生严重关节炎(50%的动物)。CD200分子(以前称为OX2)与滤泡树突状细胞等相关,参与免疫系统的免疫抑制信号的传递,以及CD200的胞外区与小鼠IgG2a相连的免疫粘附素。已有研究表明,Fe区可促进移植肾存活。在这个模型中,DBA/1小鼠在胶原免疫后间隔3天接受CD200Fc 15ug/只,没有发生关节炎。经CD200Fc处理的胶原蛋白免疫小鼠的淋巴细胞经胶原蛋白再刺激后,其培养上清液中的肿瘤坏死因子α和干扰素-γ水平显著低于PBS或正常小鼠免疫球蛋白对照组小鼠的淋巴细胞。CD200Fc处理组小鼠血清中的抗胶原免疫球蛋白含量低于对照组(相当于减少50%),相对较多的是IgG2b和IgG3,而肿瘤坏死因子α和干扰素-γ的水平低于对照组。这些数据表明,这种免疫粘附素可能在调节自身免疫性疾病方面发挥重要作用。(C)2001年爱思唯尔科学公司。
DBA/1 mice immunized with 100 mug bovine collagen type II emulsified in Freund's adjuvant, followed by booster injection in incomplete adjuvant at 18 days, develop profound arthritis (> 50% of animals) by days postinjection. The molecule CD200 (previously called OX2), associated with, among others, follicular dendritic cells, is implicated in delivery of immunosuppressive signals to the immune system, and an immunoadhesin in which the extracellular domains of CD200 were linked to a mouse IgG2a. Fe region has been shown to promote renal allograft survival. DBA/1 mice receiving 15 mug/mouse CD200Fc at 3-day intervals following immunization with collagen did not develop arthritis in this model. Lymphocytes taken from CD200Fc-treated, collagen-immunized mice produced significantly lower levels of TNF alpha and IFN-gamma in culture supernatants after restimulation in vitro with collagen, in contrast to cells taken from control mice treated with PBS or normal mouse Ig. Serum from CD200Fc-treated mice contained less anti-collagen IgG (similar to 50% reduction), with relatively more IgG2b and IgG3, and lower levels of TNF alpha and IFN-gamma, than control mice. These data indicate that this immunoadhesin may have a potent role to play in the regulation of autoimmune disorders. (C) 2001 Elsevier Science.