Aberrant positioning of trophoblast and lymphocytes in the feto-maternal interface with pre-eclampsia

Abstract

Pregnancy represents the growth of an allograft where fetal trophoblast cells evade immune rejection and invade maternal tissue. There should be a balance between fetal trophoblast and maternal immune-responsive cells and alterations in the proportion of these cells may relate to pregnancy disorders. To test this, the decidual tissue of placental bed biopsies was examined and trophoblast cells and lymphocytes were quantified morphometrically; spiral arteries were classified as unchanged, transformed or affected by acute atherosis. Normal pregnancy (n=19) was characterized by the transformation of about one half of all spiral arteries within the placental bed. We found that 40% of all lymphocytes were CD56+ uterine NK cells and 60%, CD3+ T-lymphocytes; about 30% of these were CD8+ T cells. Intrauterine growth retardation in the context of preeclampsia (n=15) was accompanied by reduced trophoblast numbers within smaller and more tortuous arteries and an increase in the proportion of CD56+ uterine NK cells and CD8+ T lymphocytes in the decidua (70% of all CD3+ cells). In the case of pre-eclampsia without fetal growth retardation (n=14) no increase in CD56+ uterine NK cells was seen, while CD8+ T lymphocytes were significantly increased compared with the normal level (50% of all CD3+ cells). Fetal growth retardation is associated with poor transformation of spiral arteries and characterized by an increase of uterine NK cells. Symptoms of pre-eclampsia are independently associated with an increase in the cytotoxic T subset of decidual lymphocytes. Pre-eclampsia and related fetal growth retardation are seemingly caused by an enhancement of the maternal cytotoxic defence against the fetal allograft.

Altered decidual leucocyte populations in the placental bed in pre-eclampsia and foetal growth restriction: a comparison with late normal pregnancy

“…However, the findings contrast with those of Stallmach et al (1999) and Bachmayer et al (2006) who reported increased numbers of CD56C cells in PE decidua compared with controls. In the absence of information on the FGR status of the PE study groups in these latter studies, use of placental bed biopsy and the avidinbiotin method, which is more sensitive than the PAP method used by Stallmach et al (1999), may also partly account for the differences in uNK cell numbers.…”

“…Studies of human decidual leucocyte populations in PE and FGR are limited. Khong (1987) reported no differences in placental bed and non-placental bed leucocyte populations in PE compared with normal-term pregnant controls while Stallmach et al (1999) reported an increase in CD8CT cells and CD56C uNK cells in decidua from women with PE. These observations were confirmed in a flow cytometric study, CD56C cells also showing an altered phenotype with a shift from the CD16KCD56C to the more cytotoxic CD16CCD56C phenotype (Wilczynski et al 2003).…”

“…Overall, therefore, the precise composition of decidual leucocytes in pregnancies complicated by PE and FGR remains controversial and unclear. This may in part be due to the different sources of decidual tissue investigated in these studies either obtained by vacuum suction of the placental bed after delivery (Eide et al 2006), attached to the placenta delivered by Caesarean section (Burk et al 2001, Wilczynski et al 2003, Lockwood et al 2006 or from placental bed biopsies (Reister et al 1999, Stallmach et al 1999, Kim et al 2007.…”

Immune cells in the placental bed

“…Increased numbers of CD4+ T lymphocytes have been reported in decidua from women with pre-eclampsia compared to age matched controls (Stallmach et al, 1999;Wilczynski et al, 2003). However, work in our laboratory demonstrated a reduction in both CD3+ and CD8+ cells in pre-eclampsia (Scaife, Innes, Searle, Robson, Bulmer; unpublished data).…”

Decidual NK Cells Alter In Vitro First Trimester Extravillous Cytotrophoblast Migration: A Role for IFN-γ

“…Preeclampsia, and the related fetal growth restriction, are interpreted as consequences of impaired trophoblast invasion (1,6). Severe reduction of trophoblast cells, in combination with a strong increase of maternal lymphocytes and dNK cells, is found in intrauterine growth restriction (7).…”