Unit for Autoimmunity and Immune Regulation, Division of Clinical Immunology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
Biol Reprod. 2010 Apr;82(4):698-705. doi: 10.1095/biolreprod.109.081208. Epub 2009 Dec 16.
In pregnancy, the decidua is infiltrated by leukocytes promoting fetal development without causing immunological rejection. Murine regulatory T (Treg) cells are known to be important immune regulators at this site. The aim of the study was to characterize the phenotype and origin of Treg cells and determine the quantitative relationship between Treg, T-helper type 1 (T(H)1), T(H)2, and T(H)17 cells in first-trimester human decidua. Blood and decidual CD4(+) T cells from 18 healthy first-trimester pregnant women were analyzed for expression of Treg-cell markers (CD25, FOXP3, CD127, CTLA4, and human leukocyte antigen-DR [HLA-DR]), chemokine receptors (CCR4, CCR6, and CXCR3), and the proliferation antigen MKI67 by six-color flow cytometry. Treg cells were significantly enriched in decidua and displayed a more homogenous suppressive phenotype with more frequent expression of FOXP3, HLA-DR, and CTLA4 than in blood. More decidual Treg cells expressed MKI67, possibly explaining their enrichment at the fetal-maternal interface. Using chemokine receptor expression profiles of CCR4, CCR6, and CXCR3 as markers for T(H)1, T(H)2, and T(H)17 cells, we showed that T(H)17 cells were nearly absent in decidua, whereas T(H)2-cell frequencies were similar in blood and decidua. CCR6(+) T(H)1 cells, reported to secrete high levels of interferon gamma (IFNG), were fewer, whereas the moderately IFNG-secreting CCR6(-) T(H)1 cells were more frequent in decidua compared with blood. Our results point toward local expansion of Treg cells and low occurrence of T(H)17 cells. Furthermore, local, moderate T(H)1 activity seems to be a part of normal early pregnancy, consistent with a mild inflammatory environment controlled by Treg cells.
在妊娠期间，蜕膜被白细胞浸润，促进胎儿发育而不引起免疫排斥。已知在这个部位，小鼠调节性 T (Treg)细胞是重要的免疫调节剂。本研究的目的是描述 Treg 细胞的表型和来源，并确定妊娠早期人类蜕膜中 Treg、T-helper 型 1 (T(H)1)、T(H)2 和 T(H)17 细胞的定量关系。分析了 18 名健康早孕孕妇的血液和蜕膜 CD4(+)T 细胞，通过六色流式细胞术检测 Treg 细胞标志物（CD25、FOXP3、CD127、CTLA4 和人类白细胞抗原-DR [HLA-DR]）、趋化因子受体（CCR4、CCR6 和 CXCR3）和增殖抗原 MKI67 的表达。Treg 细胞在蜕膜中明显富集，并表现出更同质的抑制表型，FOXP3、HLA-DR 和 CTLA4 的表达更为频繁。更多的蜕膜 Treg 细胞表达 MKI67，这可能解释了它们在胎儿-母体界面的富集。通过趋化因子受体表达谱 CCR4、CCR6 和 CXCR3 作为 T(H)1、T(H)2 和 T(H)17 细胞的标志物，我们发现 T(H)17 细胞在蜕膜中几乎不存在，而血液和蜕膜中 T(H)2 细胞的频率相似。报道分泌高水平干扰素γ (IFNG)的 CCR6(+)T(H)1 细胞较少，而中度分泌 IFNG 的 CCR6(-)T(H)1 细胞在蜕膜中比血液中更为常见。我们的结果表明 Treg 细胞的局部扩增和 T(H)17 细胞的低发生。此外，局部、适度的 T(H)1 活性似乎是正常早孕的一部分，与 Treg 细胞控制的轻度炎症环境一致。
