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Human decidual tissue contains differentiated CD8+ effector-memory T cells with unique properties

机译:人蜕膜组织含有分化的CD8 +效应记忆T细胞,具有独特的特性

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摘要

During pregnancy, maternal lymphocytes at the fetal-maternal interface play a key role in the immune acceptance of the allogeneic fetus. Recently, CD4(+)CD25(bright) regulatory T cells have been shown to be concentrated in decidual tissue, where they are able to suppress fetus-specific and nonspecific immune responses. Decidual CD8(+) T cells are the main candidates to recognize and respond to fetal HLA-C at the fetal-maternal interface, but data on the characteristics of these cells are limited. In this study we examined the decidual and peripheral CD8(+) T cell pool for CD45RA, CCR7, CD28, and CD27 expression, using nine-color flow cytometry. Our data demonstrate that decidual CD8(+) T cells mainly consist of differentiated CD45RA(-)CCR7(-) effector-memory (EM) cells, whereas unprimed CD45RA(+)CCR7(+) naive cells are almost absent. Compared with peripheral blood EM CD8(+) T cells, the decidual EM CD8(+) T cells display a significantly reduced expression of perforin and granzyme B, which was confirmed by immunohistochemistry of decidual tissue sections. Interestingly, quantitative PCR analysis demonstrates an increased perforin and granzyme B mRNA content in decidual EM CD8(+) T cells in comparison with peripheral blood EM CD8(+) T cells. The presence of high levels of perforin and granzyme B mRNA in decidual EM T cells suggests that decidual CD8(+) T cells pursue alternative means of EM cell differentiation that may include a blockade of perforin and granzyme B mRNA translation into functional perforin and granzyme B proteins. Regulation of decidual CD8(+) T cell differentiation may play a crucial role in maternal immune tolerance to the allogeneic fetus
机译:在怀孕期间,胎儿-母亲界面处的母亲淋巴细胞在同种异体胎儿的免疫接受中起关键作用。最近,已显示CD4(+)CD25(亮)调节性T细胞集中在蜕膜组织中,在那里它们能够抑制胎儿特异性和非特异性免疫反应。蜕膜CD8(+)T细胞是在胎儿-母亲界面识别和响应胎儿HLA-C的主要候选对象,但有关这些细胞特性的数据有限。在这项研究中,我们使用九色流式细胞仪检查了蜕膜和外周CD8(+)T细胞池的CD45RA,CCR7,CD28和CD27表达。我们的数据表明,蜕膜CD8(+)T细胞主要由分化的CD45RA(-)CCR7(-)效应记忆(EM)细胞组成,而未启动的CD45RA(+)CCR7(+)幼稚细胞几乎不存在。与外周血EM CD8(+)T细胞相比,蜕膜EM CD8(+)T细胞显示穿孔素和颗粒酶B的表达显着降低,这已通过蜕膜组织切片的免疫组织化学证实。有趣的是,定量PCR分析表明与外周血EM CD8(+)T细胞相比,蜕膜EM CD8(+)T细胞中穿孔素和颗粒酶B mRNA的含量增加。蜕膜EM T细胞中高水平的穿孔素和颗粒酶B mRNA的存在表明,蜕膜CD8(+)T细胞正在寻求EM细胞分化的替代方法,其中可能包括阻断穿孔素和颗粒酶B mRNA转化为功能性穿孔素和颗粒酶B的过程。蛋白质。蜕膜CD8(+)T细胞分化的调控可能在母体对同种异体胎儿的免疫耐受中起关键作用

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