Maternal Foxp3 Expressing CD4+ CD25+ and CD4+ CD25- Regulatory T-Cell Populations are Enriched in Human Early Normal Pregnancy Decidua: A Phenotypic Study of Paired Decidual and Peripheral Blood Samples
Maternal Foxp3 Expressing CD4+ CD25+ and CD4+ CD25- Regulatory T-Cell Populations are Enriched in Human Early Normal Pregnancy Decidua: A Phenotypic Study of Paired Decidual and Peripheral Blood Samples
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DOI：
10.1111/j.1600-0897.2011.01046.x
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发表时间：
2011-07-01
影响因子：
3.6
通讯作者：
Mincheva-Nilsson, Lucia
中科院分区：
文献类型：
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作者：
Dimova, Tanya;Nagaeva, Olga;Mincheva-Nilsson, Lucia
问题调节性T细胞(Treg细胞)是CD4(+)T细胞的一个小亚群，通过免疫抑制来维持耐受，被认为是胎儿半异基因移植物存活的贡献者。采用免疫组织化学、免疫荧光、流式细胞仪和实时定量RT-PCR等方法，对正常早孕妇女蜕膜和外周血(PB)及非妊娠妇女外周血(PB)中的Treg细胞进行了检测。蜕膜中有3个Foxp3(+)细胞群，即CD4(+)CD25(++)Foxp3(+)、CD4(+)CD25(+)Foxp3(+)和CD4(+)CD25(-)Foxp3(+)。相比之下，孕妇和非孕妇之间的循环Treg细胞数量没有统计上的显著差异。Foxp3(+)细胞表达与Treg表型一致的表面分子CD45RO、CTLA-4、CD103、Neuropilin-1、LAG-3、CD62L和转化生长因子β1。在配对样本中，CD4(+)CD25(-)Foxp3(+)细胞的数量比外周血中丰富了10倍，这是以前在人类蜕膜中没有描述的。其细胞因子表达与Th3类似，而Foxp3mRNA在蜕膜中的表达水平稳定，与CD4(+)CD25(+)Treg细胞的表达水平相当，提示大多数CD4(+)CD25(-)Foxp3(+)细胞可能是未成熟的Treg细胞。
ProblemRegulatory T cells (Treg cells), a small subset of CD4(+) T cells maintaining tolerance by immunosuppression, are proposed contributors to the survival of the fetal semiallograft. We investigated Treg cells in paired decidual and peripheral blood (PB) samples from healthy women in early pregnancy and PB samples from non-pregnant women.Method of studyDistribution, location, cytokine mRNA, and phenotype were assessed in CD4(+) CD25(+) Treg cells from paired samples using immunohistochemistry, immunofluorescence, flow cytometry, and real-time quantitative RT-PCR.ResultsThe presence and in situ distribution of CD4(+) Foxp3(+) Treg cells in decidua are hereby demonstrated for the first time. Three Foxp3(+) cell populations, CD4(+) CD25(++) Foxp3(+), CD4(+) CD25(+) Foxp3(+), and CD4(+) CD25(-) Foxp3(+), were enriched locally in decidua. In contrast, no statistically significant difference in numbers of circulating Treg cells between pregnant and nonpregnant women was found. The Foxp3(+) cells expressed the surface molecules CD45RO, CTLA-4, CD103, Neuropilin-1, LAG-3, CD62L, and TGF beta 1 mRNA consistent with Treg phenotype. The population of CD4(+) CD25(-) Foxp3(+) cells, not described in human decidua before, was enriched 10-fold compared with PB in paired samples. Their cytokine expression was often similar to Th3 profile, and the Foxp3 mRNA expression level in CD4(+) CD25(-) cells was stable and comparable to that of CD4(+) CD25(+) Treg cells implying that the majority of CD4(+) CD25(-) Foxp3(+) cells might be naive Treg cells.Conclusion(i) There is a local enrichment of Treg cells in decidua (ii) The exclusive accumulation of decidual CD4(+) CD25(-) Foxp3(+) cells suggests an additional reservoir of Foxp3(+) naive Treg cells that can be converted to 'classical' Treg cells in uterus.