Schwede S, Alfer J, von Rango U
Department of Molecular and Cellular Anatomy, Medical School, RWTH Aachen, Wendlingweg 2, 52074 Aachen, Germany.
Department of Pathology, Kaufbeuren-Ravensburg, Dr.-Gutermann-Str. 6, 87600 Kaufbeuren/ Elisabethenstr. 19, 88212 Ravensburg, Germany; Department of Pathology, Roonstraße 30, 52351 Düren, Germany.
Placenta. 2014 Jun;35(6):378-85. doi: 10.1016/j.placenta.2014.03.004. Epub 2014 Mar 21.
Primary infertility, miscarriage, and preeclampsia have been correlated with reduced numbers of regulatory T-cells (Treg) suggesting that decreased extravillous trophoblast (EVT) invasion originates from inadequate EVT tolerance. In contrast increased numbers of Treg-cells may be responsible for over-invasion of EVT. As the maturation status of dendritic cells (DC) influences T-cell behavior (tolerance or immune activation), altered relation between immature and mature DCs may also influence EVT invasion.
Paraffin-embedded specimens of placenta accreta/increta (Pc; n = 11) and healthy intrauterine pregnancy (IUG; n = 18) were double-stained for cytokeratin and CD45, CD68, CD56, CD20, CD3, or CD8 as well as FoxP3/CD4 and FoxP3/CD8 and single-stained for CD4, CD25, FoxP3, CD209, Dec205 and CD83. Quantification of the leukocyte subpopulations was performed for decidua parietalis and basalis as characterized by cytokeratin-positive EVT. Statistical analysis was performed by using the Mann-Whitney test.
There were significantly fewer CD4(+) cells in Pc than in IUG. Concerning the Treg-markers, FoxP3(+) cells are significantly increased. CD25(+) cells showed a small non-significant increase in Pc in comparison to IUG. Concerning dendritic cells, immature non-activated CD209(+) DCs were significantly decreased in Pc while immature activated CD205(+) DCs were slightly but non-significantly increased. Mature activated CD83(+) DC were non-significantly decreased in IUG vs Pc.
The increased number of Treg-cells in Pc suggests significance for these cells in the regulation of trophoblast invasion. Their adequate interaction with other lymphocyte populations (e.g. adequately maturated dendritic cells) may be one mechanism to assure controlled EVT invasion.
原发性不孕、流产和先兆子痫与调节性T细胞(Treg)数量减少有关,这表明绒毛外滋养层细胞(EVT)侵袭减少源于EVT耐受性不足。相反,Treg细胞数量增加可能导致EVT过度侵袭。由于树突状细胞(DC)的成熟状态会影响T细胞行为(耐受性或免疫激活),未成熟和成熟DC之间关系的改变也可能影响EVT侵袭。
对胎盘植入/穿透(Pc;n = 11)和正常宫内妊娠(IUG;n = 18)的石蜡包埋标本进行细胞角蛋白与CD45、CD68、CD56、CD20、CD3或CD8以及FoxP3/CD4和FoxP3/CD8的双重染色,并对CD4、CD25、FoxP3、CD209、Dec205和CD83进行单染色。以细胞角蛋白阳性的EVT为特征,对子宫壁蜕膜和基底蜕膜中的白细胞亚群进行定量分析。采用曼-惠特尼检验进行统计分析。
Pc组中CD4(+)细胞明显少于IUG组。关于Treg标志物,FoxP3(+)细胞显著增加。与IUG组相比,Pc组中CD25(+)细胞有小幅但无统计学意义的增加。关于树突状细胞,Pc组中未成熟的非活化CD209(+) DC显著减少,而未成熟活化的CD205(+) DC略有增加但无统计学意义。与Pc组相比,IUG组中成熟活化的CD83(+) DC无统计学意义的减少。
Pc组中Treg细胞数量增加表明这些细胞在滋养层侵袭调节中具有重要意义。它们与其他淋巴细胞群体(如充分成熟的树突状细胞)的适当相互作用可能是确保EVT侵袭得到控制的一种机制。