Reproductive Immunology Group, Institute of Medical Immunology, Charité, Universitätsmedizin, Berlin, Germany.
Am J Reprod Immunol. 2010 Mar 1;63(3):200-8. doi: 10.1111/j.1600-0897.2009.00793.x. Epub 2010 Jan 4.
Mammalian pregnancy is a state of immunological tolerance and CD4(+) CD25(+) regulatory T cells (Treg) contribute to its maintenance. Knowing that Treg act in an antigen-specific way during pregnancy, we hypothesized that they are generated after maternal immune cells encounter paternal antigens.
We mated wild type females with transgenic green fluorescent protein (GFP) males in an allogenic setting and killed them on different days of pregnancy.
Presence of paternal and maternal MHC class II(+) cells in vaginal lavage on day 0.5 of pregnancy was confirmed. Thus, antigen presentation may take place early during pregnancy in the periphery either by the direct or indirect pathways. Foxp3(+) cells known to have regulatory activity could be detected on day 2 of pregnancy in lymph nodes and shortly after implantation at the fetal-maternal interface.
Our data suggest that paternal antigens are processed early during pregnancy, which leads to the generation of Treg. The continuous release of placental antigens into the maternal circulation allows the maintenance of a Treg population which is specific for paternal antigens and mediates tolerance toward the semi-allogeneic fetus until the time point of birth.
哺乳动物妊娠是一种免疫耐受状态，CD4(+) CD25(+) 调节性 T 细胞（Treg）有助于维持这种状态。由于 Treg 在妊娠期间具有抗原特异性作用，我们假设它们是在母体免疫细胞遇到父系抗原后产生的。
我们将野生型雌性与转基因 GFP 雄性在同种异体环境中交配，并在妊娠的不同天数将它们杀死。
在妊娠第 0.5 天的阴道冲洗液中证实存在父系和母系 MHC 类 II(+) 细胞。因此，抗原呈递可能在妊娠早期通过直接或间接途径在外周发生。在妊娠第 2 天可以在淋巴结中检测到具有调节活性的 Foxp3(+)细胞，并且在植入后不久就在胎儿-母体界面处检测到。
我们的数据表明，父系抗原在妊娠早期被加工，这导致 Treg 的产生。胎盘抗原不断释放到母体循环中，允许针对父系抗原的 Treg 群体的维持，并介导对半同种异体胎儿的耐受，直到分娩时刻。
