FOXP3 調節性 T 細胞以及 CD8 T 細胞聚集在人類正常與無胚胎懷孕子宮內膜組織中的分佈情形
Distribution of FOXP3+ Regulatory T Cells and CD8+ T Cell-Rich Lymphoid Aggregates in Decidua from Human Normal and Anembryonic Pregnancies
Date Issued
2007
Date
2007
Author(s)
Wu, Yu-Jung
DOI
en-US
Abstract
In order to have successful implantation and development of the fetus, the maternal immune system must be modified by several appropriate regulations in mammal. Besides the immunoregulation of sexual hormones, the immune cells in human decidua (endometrial tissue) during pregnancy have some different characteristics from those in other human tissues. CD4+CD25+ regulatory T cell (Treg) which is a subset of CD4+ regulatory T cells plays a critical role in the modulation of immune response. FOXP3 is a key molecule predominantly restricted to CD4+CD25+ Treg cells. Recently, some human and mice experiments reported that the population of CD4+CD25+ Treg cells increased during pregnancy and these Treg expressed foxp3 mRNA. However, most of these studies investigated the population of CD4+CD25+ Treg cells by flow cytometry. However, the physiological role of FOXP3+ Treg cells and their interactions with other immune cells in the endometrial microenvironment remains unknown. In order to understand this issue in normal and anembryonic human pregnancies, we used immunostaining method to detect FOXP3+ cells and indicated that the percentage of FOXP3+ cells in CD3+ cells was higher in decidua from normal pregnancies compare to those from anembryonic pregnancies. We also noted that the FOXP3+ cells were close to a special structure, CD8+ T cell-rich lymphoid aggregates, in the decdual tissues. Combined with cell markers, CD8, CD4, CD11b, CD19, CD56, we further evidenced the distribution of FOXP3+ cells and other immune cells in lymphoid aggregates. Our data indicate that the CD8+ T cell-rich lymphoid aggregates contain few B cells in the center whereas CD8+ T cells forms the main structure of the lymphoid aggregates. CD4+ T cells are few and scattered, uNK cells surround the CD8+ T cell-rich lymphoid aggregates and CD11b+ macrophages are outside. We also found that FOXP3+ Tregs were around the lymphoid aggregates and sometimes contact to CD8+ T cells. By Granzyme B staining, we suggested that granzyme B may contribute to the regulation between FOXP3+ Treg and CD8+ T cells. Although CD8+ T cells and uNK cells in lymphoid aggregates can express cytotoxic factors such as Granzyme A and Perforin, the Granzyme A and Perforin expressions of CD8+ cells and NK cells outside the CD8+ T cell-rich lymphoid aggregates was less in normal pregnancies compares to that in anembryonic pregnancies. Additionally, there are larger and well organizing CD8+ T cell-rich lymphoid aggregates in normal pregnancies. We speculate that this restriction of CD8+ T cells by lymphoid aggregates may contribute to the immunoregulation in the human decidual tissues. And in other area beside lymphoid aggregates in the normal decidua, there are also some mechanisms to reduce the inflammatory response. By this research, we hope to understand more about the complicated microenvironment during pregnancy and that mechanisms may promote successful implantation and fetus development.
Subjects
調節性 T 細胞
CD8 T 細胞聚集
子宮內膜
FOXP3
CD8+ T Cell-Rich Lymphoid Aggregates
Decidua
Type
other
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