Proportion of peripheral blood and decidual CD4+ CD25bright regulatory T cells in pre-eclampsia

Abstract

Summary CD4+ CD25 bright regulatory T (Treg) cells have been identified as a principle regulator of tolerance during pregnancy. In the setting of pre-eclampsia, however, little is known about the dynamics of these cells. In the current study, we determined CD4 + CD25 bright Treg cells in the peripheral blood using flow cytometry and forkhead box P3 (FoxP3 + ) cells at the placental bed using immunohistochemical staining. Peripheral blood mononuclear cells (PBMC) of 38 pre-eclamptic cases (17 cases Japanese, 21 cases Polish), 40 normal late pregnancy subjects (20 subjects Japanese, 20 subjects Polish), and 21 non-pregnant healthy controls (10 subjects Japanese, 11 subjects Polish) were included. We found the percentage of CD25 bright cells within the CD4+ T cell population in PBMC was reduced significantly in both Japanese and Polish pre-eclamptic cases than in normal pregnancy subjects (P < 0·001) and non-pregnant healthy controls (P < 0·001). Also, the percentage of FoxP3+ cells within CD3 + T cells in the placental bed biopsy samples of pre-eclamptic cases were decreased compared to those in normal pregnancy subjects. These findings suggest that a decreased number of Treg cells was present in pre-eclampsia, and these changes might break the maternal tolerance to the fetus.

Systemic reduction of functionally suppressive CD4dimCD25highFoxp3+ Tregs in human second trimester pregnancy is induced by progesterone and 17β-estradiol

“…Importantly, we showed that this population was non-suppressive and since it did not expand in response to neither progesterone nor 17β-estradiol, the expansion of this population must be caused by other pregnancy-related changes, possibly by the presence of fetal alloantigens. Previous studies in humans have shown CD4 + CD25 high Treg frequencies (expressed as percentage of CD4 + ) ranging from 8 to 17.5% in pregnant and 4.4-10% in non-pregnant women (19,(21)(22)(23) Tregs in pregnancy need re-evaluation. Furthermore, we stress the importance of using a strict Treg gate, preferably based on co-expression of several Treg markers, to obtain reliable data not only in pregnancy, but also in other immune challenging conditions such as autoimmune diseases and transplantations.…”

“…However, the importance of Tregs in maintenance of human pregnancy in vivo is far from settled. Studies in humans have suggested that there is an increase in the CD4 + CD25 high population during normal pregnancy, most apparently at the fetal-maternal interface (19)(20)(21) but also in the circulation (19,(21)(22)(23).…”

Immune cells in the placental bed

“…Yang et al (2008) have reported reduced proportions of CD4+ CD25bright cells in decidua in unexplained recurrent miscarriage compared with controls; whereas there was a significant difference between the percentage of CD25bright cells in the decidual and peripheral blood CD4+ populations, no such difference was noted in recurrent miscarriage subjects. Reduced numbers of CD25bright CD4+ regulatory T lymphocytes have also been reported in both peripheral blood and decidua in pre-eclampsia compared with normal pregnancy controls (Sasaki et al, 2007).…”

REVIEW ARTICLE: Th1/Th2/Th17 and Regulatory T‐Cell Paradigm in Pregnancy

“…17,37,38 Recent reports described decreased numbers of Treg cells in preeclampsia, 53,54 although two other articles found stable Treg cells in preeclampsia. 55,56 However, the sample number was too small in one study, 56 and the other study 55 Recently, the developmental and functional links between induced Treg (iTreg) cells and Th17 cells have been reported.…”