Thuere Catharina, Zenclussen Maria Laura, Schumacher Anne, Langwisch Stefanie, Schulte-Wrede Ursula, Teles Ana, Paeschke Steffen, Volk Hans-Dieter, Zenclussen Ana Claudia
Institute of Medical Immunology, Charité, Universitätsmedizin, Berlin, Germany.
Am J Reprod Immunol. 2007 Dec;58(6):514-23. doi: 10.1111/j.1600-0897.2007.00538.x.
The semi-allogeneic fetus is usually tolerated by the maternal immune system. This was proposed to be modulated by CD4+CD25+foxp3+ regulatory T cells (Treg). We aimed to determine the kinetics of Treg during murine gestation and investigate whether changes in Treg levels respond to hormonal variations during pregnancy or generated changes in the local indolamine dioxygenase (IDO) expression.
We included in our studies the well-known CBA/JxDBA/2J abortion-prone combination using CBA/JxBALB/c as controls. CBA/JxC57/BL6 and BALB/cxC57/BL6 were included as further controls. Animals were killed on days 0, 2, 5, 8, 10, and 12 of pregnancy to measure the levels of Treg, pregnancy-related hormones and IDO expression.
A Treg augmentation in normal pregnancy combinations could be observed on day 2 in several organs contrary to the observations made in abortion-prone mice. No differences in hormonal levels could be seen among all groups. IDO was expressed exclusively in placenta starting from day eight, showing no variations among the groups.
Differences in Treg levels and pregnancy outcome do not correlate with changes in hormonal levels. In addition, as Treg augmentation takes place early and it is observed mainly in the decidual component of the fetal-maternal interface, IDO does not seem to be the pathway underlying Treg protective activity as proposed for humans.
半同种异体胎儿通常能被母体免疫系统所耐受。有人提出这是由CD4+CD25+foxp3+调节性T细胞(Treg)介导的。我们旨在确定小鼠妊娠期Treg的动力学,并研究Treg水平的变化是否对孕期激素变化作出反应,或者是否引起局部吲哚胺双加氧酶(IDO)表达的改变。
我们在研究中纳入了众所周知的易发生流产的CBA/JxDBA/2J组合,并以CBA/JxBALB/c作为对照。还纳入了CBA/JxC57/BL6和BALB/cxC57/BL6作为进一步的对照。在妊娠第0、2、5、8、10和12天处死动物,以测量Treg水平、妊娠相关激素水平和IDO表达。
与易发生流产的小鼠不同,在正常妊娠组合中,第2天在多个器官中可观察到Treg增加。所有组之间激素水平未见差异。从第8天开始,IDO仅在胎盘中表达,各组之间无变化。
Treg水平的差异和妊娠结局与激素水平的变化无关。此外,由于Treg增加发生在早期,且主要在母胎界面的蜕膜成分中观察到,因此IDO似乎并非如对人类所提出的那样是Treg保护活性的潜在途径。