Identification of an Expressed Truncated Form of CD200, CD200tr, Which is a Physiologic Antagonist of CD200-Induced Suppression
Identification of an Expressed Truncated Form of CD200, CD200tr, Which is a Physiologic Antagonist of CD200-Induced Suppression
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DOI：
10.1097/tp.0b013e318186fec2
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发表时间：
2008-10-27
期刊：
影响因子：
6.2
通讯作者：
Gorczynski, Reginald M.
中科院分区：
文献类型：
--
作者：
Chen, Zhiqi;Chen, Dang-Xiao;Gorczynski, Reginald M.
背景。早期研究表明，细胞表面表达的 CD200 或该分子的可溶形式，在与受体 (CD200R) 结合后，可以在许多生物系统中诱导免疫抑制，并促进移植物接受的增加。许多研究小组已报道 CD200 的 NH2 末端区域对于与 CD200R 的相互作用至关重要。方法。全长免疫抑制诱导分子 CD200 的截短形式代表 mRNA 剪接变体 CD200(tr) 的翻译，在 CHO 细胞和转导细胞中表达，用于产生 CD200(tr) 独有的 mAb。这些单克隆抗体和全长 CD200 单克隆抗体用于记录全长 CD200 和 CD200(tr) 在脂多糖刺激的树突细胞 (DC) 上的生理表达。研究了可溶形式的 CD200 和 CD200(tr)（均与鼠 IgG2aFc 连接）在体外（混合白细胞培养物）或体内（皮肤移植排斥）单独或组合抑制同种异体免疫反应的能力。结果。表达CD200(tr)的CHO细胞抑制了向培养物中添加可溶性CD200 (CD200Fc)后观察到的混合白细胞反应的抑制。此外，通过将截短的CD200的胞外结构域与鼠IgG2a Fc区融合而制备的可溶形式的CD200(tr)可以以竞争性方式阻断CD200Fc介导的对混合白细胞反应中诱导的细胞毒性T淋巴细胞的抑制，以及脂多糖刺激的脾产生的肿瘤坏死因子-α的抑制。 细胞和同种异体皮肤移植体内排斥反应。结论。综上所述，我们的数据支持这样的假设：CD200的表达剪接变体CD200(tr)是CD200的生理拮抗剂。
Background. Earlier studies have indicated that cell surface expressed CD200, or a soluble form of this molecule, can induce immunosuppression in a number of biological systems, and promote increased graft acceptance, after binding to receptors (CD200Rs). Many groups have reported that the NH2-terminal region of CD200 is crucial for interaction with CD200R.Methods. A truncated form of the full-length, immunosuppression-inducing molecule, CD200, representing translation of an mRNA splice variant, CD200(tr), was expressed in the CHO cells and the transduced cells used to produce mAbs unique to CD200(tr). These mAbs, and mAbs to full-length CD200, were used to document Physiologic expression of full-length CD200 and CD200(tr) on lipo polysaccharide-stimulated dendritic cells (DCs). The ability of a soluble form of CD200 and CD200(tr), each linked to a murine IgG2aFc, to suppress allogeneic immune responses in vitro (mixed leukocyte cultures) or in vivo (skin graft rejection) alone, or in combination, was studied.Results. CHO cells expressing CD200(tr) inhibited the suppression of mixed leukocyte reactions seen after addition of soluble CD200 (CD200Fc) to culture. In addition, a soluble form of CD200(tr) prepared by fusing the extracellular domain of the truncated CD200 to a murine IgG2a Fc region, could block in a competitive fashion the CD200Fc-mediated suppression of cytotoxic T lymphocyte induced in mixed leukocyte reactions, of tumor necrosis factor-alpha produced by lipopolysaccharide-stimulated splenic cells, and of allogeneic skin graft rejection in vivo.Conclusion. Taken together our data support the hypothesis that an expressed splice variant of CD200, CD200(tr), is a physiologic antagonist of CD200.