Expression of a CD200 Transgene Is Necessary for Induction but Not Maintenance of Tolerance to Cardiac and Skin Allografts
Expression of a CD200 Transgene Is Necessary for Induction but Not Maintenance of Tolerance to Cardiac and Skin Allografts
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DOI：
10.4049/jimmunol.0900200
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发表时间：
2009-08-01
影响因子：
4.4
通讯作者：
Boudakov, Ivo
中科院分区：
文献类型：
--
作者：
Gorczynski, Reginald M.;Chen, Zhiqi;Boudakov, Ivo
CD200是Ig超基因家族的2型跨膜分子，可以在许多生物系统中诱导免疫抑制，并在与其受体（CD200Rs）结合后促进移植物接受度的增加。在多西环素诱导的启动子的控制下，过表达CD200的转基因小鼠很容易诱导皮肤和心脏异体移植物接受，这两种启动子都与一些与T细胞亚群分化改变相关的基因mrna的转染表达增加有关，包括gta -3、2型细胞因子（IL-4、IL-13）、GITR和Foxp3。有趣的是，移植后约1.2-15天，诱导转基因CD200表达可以停止（通过停用强力霉素），对移植物存活无明显影响。然而，通过抗CD200单抗中和所有CD200表达（包括内源性CD200表达）导致移植物损失，引入急性炎症刺激（LPS， 10 μ g/小鼠，通过i.p.注射）也是如此。我们的结论是，即使是明显稳定接受的同种异体组织移植物，强烈的炎症刺激破坏免疫调节平衡也会导致移植物损失。免疫学杂志，2009,33(3):1560-1568。
CD200, a type 2 transmembrane molecule of the Ig supergene family, can induce immunosuppression in a number of biological systems, as well as promote increased graft acceptance, following binding to its receptors (CD200Rs). Skin and cardiac allograft acceptance are readily induced in transgenic mice overexpressing CD200 under control of a doxycycline-inducible promoter, both of which are associated with increased intragraft expression of mRNAs for a number of genes associated with altered T cell subset differentiation, including GATA-3, type 2 cytokines (IL-4, IL-13), GITR, and Foxp3. Interestingly, some 1.2-15 days after grafting, induction of transgenic CD200 expression can be stopped (by doxycycline withdrawal), without obvious significant effect on graft survival. However, neutralization of all CD200 expression (including endogenous CD200 expression) by anti-CD200 mAb caused graft loss, as did introduction of an acute inflammatory stimulus (LPS, 10 mu g/mouse, delivered by i.p. injection). We conclude that even with apparently stably accepted tissue allografts, disruption of the immunoregulatory balance by an intense inflammatory stimulus can cause graft loss. The Journal of Immunology, 2009, 183: 1560-1568.