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首页> 外文期刊>Biology of Reproduction: Offical Journal of the Society for the Study of Reproduction >Blockade of CD86 signaling facilitates a Th2 bias at the maternal-fetal interface and expands peripheral CD4(+)CD25(+) regulatory T cells to rescue abortion-prone fetuses
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Blockade of CD86 signaling facilitates a Th2 bias at the maternal-fetal interface and expands peripheral CD4(+)CD25(+) regulatory T cells to rescue abortion-prone fetuses

机译：封锁CD86信号促进Th2偏见在母胎界面和扩展外围CD4 (+) CD25(+)调节性T细胞救援abortion-prone胎儿

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摘要

Intervention in B7 (CD80/CD86)/B7-Iigand (CD28/CTLA-4) pathways is an effective way of preventing unwanted immune responses, such as allograft rejection. Pregnancy maintenance represents maternal tolerance to the fetal allograft, which is accompanied by a type 2 helper cell (Th2) bias at the maternal-fetal interface. Here, the costimulatory signal of CD86 was selectively blocked, and that of CD80 was kept unimpaired by administration of anti-murine CD86 monoclonal antibody at the early gestational stage in abortion-prone CBA/J X DBA/2 matings and normal pregnant CBA/J X BALB/c matings. It was demonstrated that in vivo blockade of CD86 costimulation could suppress maternal immune attack to the fetus by shifting cytokines from Th1 predominance to Th2 bias at the maternal-fetal interface, and expanding peripheral CD4(+)CD25(+) regulatory T cells, which play an important role in the development and maintenance of maternal-fetal tolerance. Furthermore, the expression of CD28 and its ligands CD80/CD86 on peripheral lymphocytes was down-regulated, whereas that of CTLA-4 was up-regulated, which might facilitate the suppressive effect of CD4(+)CD25(+) regulatory T cells on the alloreactive T cells. The maternal-fetal immunotolerance induced by CD86 blockade decreased fetal resorption in CBA/J X DBA/2 matings, but did not affect normal pregnant CBA/J X BALB/c matings. These results suggest that selective blockade of CD86 costimulation leads to maternal immune tolerance to embryo antigen, and might contribute to a rational immunoregulatory regimen for recurrent spontaneous abortion.
机译：干预B7 (CD80 / CD86) / B7-Iigand(CD28 / CTLA-4)途径是一种有效的方法防止不必要的免疫反应,如同种异体移植物排斥反应。胎儿代表母性的宽容同种异体移植物,伴随着2型辅助细胞(Th2)偏见在母胎接口。是选择性地阻止,CD80的吗一直没有anti-murine管理局CD86单克隆抗体在早期妊娠阶段abortion-prone CBA / J X DBA / 2交配正常怀孕的CBA / J X BALB / c交配。表明体内CD86的封锁聚集有关可能抑制母体免疫攻击通过将细胞因子从胎儿Th1 Th2偏见的优势母胎界面,和扩大外围CD4 (+) CD25 +调节性T细胞,在发展中发挥着重要的作用和维护母胎宽容。此外,CD28的表达及其配体CD80 / CD86外周淋巴细胞衰减,而CTLA-4差异,这可能促进CD4(+)的抑制效应CD25调节性T (+)细胞alloreactive T细胞。由CD86母胎免疫耐受诱导封锁减少胎儿吸收在CBA / J XDBA / 2交配,但并不影响正常怀孕CBA / J X BALB / c交配。选择性CD86聚集有关的封锁导致母体胚胎免疫耐受抗原,可能导致一个理性免疫调节疗法对复发性自然流产。

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