Page 1138 - Veterinary Immunology, 10th Edition

on the trophoblast before day 120 gestation. Equine trophoblast
VetBooks.ir cells also appear to have reduced class I expression.

NK cells predominate in the placenta, especially early in
pregnancy. Over time, they gradually decline and are replaced by T

cells that predominate at term. These NK cells belong to a distinct
uterine subtype called uNK cells. uNK cells, also called endometrial
gland cells, have been described in rodents, bats, pigs, and horses.
They are not usually cytotoxic but they secrete large amounts of

chemokines and cytokines. These NK cells also promote immune
tolerance by suppressing Th17 cells by releasing IFN-γ.
In the hemochorial placenta found in humans and other primates,
the uNK cells release angiogenic factors that remodel the spiral

arteries located within the uterus to increase their diameter, and
thus increase placental blood flow as the fetus grows. If they fail to
do this, the blood flow to the fetus is insufficient and results in
preeclampsia or miscarriage.

Treg cells play an important role in preventing fetal rejection.
Estrogen treatment and pregnancy both induce FoxP3 expression,
as does seminal plasma, and help promote Treg production.
Trophoblast cells also secrete IDO, which blocks Th1 and Th17

responses and promotes apoptosis of cytotoxic T cells. Inhibitors of
IDO permit maternal rejection of allogeneic fetuses in mice. Treg
cells upregulate IDO expression in dendritic cells. In addition, IDO
induces trophoblast HLA-G expression, suggesting that these

molecules interact to maintain pregnancy. In humans, substantial
numbers of maternal T cells cross the placenta to reside in fetal
lymph nodes. These induce Treg cells that suppress maternal
responses to paternal antigens probably through IL-10 production

while at the same time suppressing production of Th1, Th2, and
Th17 cells.
A population of profoundly immunosuppressive cells called
myeloid-derived suppressor cells (MDSCs) accumulates in the

uterus of pregnant mice and women. They suppress T cell
activation and function. The presence of these cells down-regulates
T cell L-selectin expression and so reduces the ability of naïve T
cells to enter lymph nodes and become activated. They appear to be
of critical importance in maintaining pregnancy in mice. MSDCs are

an important cause of the immunosuppression that occurs in some

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