Regulatory T cells induce a privileged tolerant microenvironment at the fetal-maternal interface
Regulatory T cells induce a privileged tolerant microenvironment at the fetal-maternal interface
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DOI：
10.1002/eji.200535428
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发表时间：
2006-01-01
影响因子：
5.4
通讯作者：
Volk, HD
中科院分区：
文献类型：
--
作者：
Zenclussen, AC;Gerlof, K;Volk, HD
怀孕期间免疫耐受的机制尚不清楚。在这方面，Treg似乎在调节母体对胎儿的耐受性方面发挥着重要作用。在观察到有流产倾向的小鼠中 T 调节细胞 (Treg) 数量和功能减少后，我们提出 T 调节细胞 (Treg) 在避免胎儿免疫排斥方面发挥着至关重要的作用。我们通过将妊娠诱导的 Treg 移植到易流产小鼠体内，进一步证实了 Treg 在妊娠期间的保护作用，从而防止了排斥反应。在这里，我们分析了 Treg 介导的保护机制。正如预期的那样，Treg 疗法预防了流产，同时扩大了外周和胸腺 Treg 群体。令人惊讶的是，治疗后 Th1 细胞因子 IFN-γ 和 TNF-α 的蜕膜水平并未降低。有趣的是，Treg移植后，母胎界面处的白血病抑制因子、TGF-β和血红素加氧酶1的mRNA水平显着上调，而吲哚胺2,3-双加氧酶的水平保持不变。我们的数据表明，Treg 治疗不能阻止 T 细胞浸润或高 Th1 水平，但能够在胎儿-母体界面创造一个特殊的耐受性微环境，进一步揭示参与妊娠耐受性的分子机制。
The mechanisms underlying immune tolerance during pregnancy are poorly understood. In this regard, Treg seem to play an important role in mediating maternal tolerance to the fetus. We proposed a crucial role of T regulatory cells (Treg) in avoiding immunological rejection of the fetus after observing diminished number and function of Treg in abortion-prone mice. We further confirmed the protective role of Treg during pregnancy by transferring pregnancy-induced Treg into abortion-prone mice, which prevented rejection. Here, we analyzed the mechanisms involved in Treg-mediated protection. As expected, Treg therapy prevented abortion, while expanding the peripheral and thymic Treg population. Surprisingly, the decidual levels of the Th1 cytokines IFN-gamma and TNF-alpha were not diminished after therapy. Interestingly, the mRNA levels of leukemia inhibitory factor, TGF-beta and heme oxygenase-1 at the fetal-maternal interface were dramatically up-regulated after Treg transfer, while the levels of indolamine 2,3-dioxygenase remained unchanged. Our data suggest that Treg treatment can not prevent T cell infiltration or high Th1 levels but is able to create a privileged tolerant microenvironment at the fetal-maternal interface, further shedding light onto the molecular mechanisms involved in pregnancy tolerance.