Problem: The immune regulation at the fetal-maternal interface
is crucial for establishing a healthy pregnancy as the mother must
tolerate the semi-allogeneic fetus, while simultaneously being alert
to protect both the mother and the fetus from pathogens. An
imbalance in the immune regulation might have an important role
in unexplained early pregnancy disorders. The decidual natural killer
(dNK) cells comprise about 50-90 % of the decidual lymphocytes in
the first trimester. Decidual NK cells secrete cytokines, angiogenic
factors and growth factors, and they may play a key role for the
development of the placenta. The majority of the circulating
peripheral NK cells are cytotoxic with a CD56dimCD16+ phenotype.
In contrast, the majority of the dNK cells are CD56brightCD16-, and
are less cytotoxic and upon balanced activation seem to secrete
factors important for placentation. The cytokine interleukin-15 (IL-
15) is also present in the decidualized endometrium of the uterus. In
the present study, we investigated a possible shift from a peripheral
CD56dimCD16+ NK cell phenotype towards the CD56brightCD16-
decidual NK cell phenotype induced by trophoblast cells with the
choriocarcinoma cell line JEG-3 as a model, or by IL-15, or by both.
Method of Study: Peripheral blood mononuclear cells (PBMCs)
were isolated from buffy coats from 15 healthy, non-pregnant
women n (<40 years). The PBMCs were incubated in co-cultures
together with a monolayer of the human trophoblast-derived chor-
iocarcinoma cell line JEG-3 with or without IL-15 for six days.
Natural killer cell subpopulations in the PBMCs were analyzed by
flow cytometry for the markers CD3, CD14, CD20, CD56, CD16 at
day 0 and day 6. Natural killer cells were sub-grouped according to
the expression of CD56 and CD16,and analyzed for surface expres-
sion of various receptors at day 0 and day 6. JEG-3 cells were
analyzed by flow cytometry for the expression of human leukocyte
antigens (HLA) (HLA-C, HLA-E, HLA-F and HLA-G).
Results: PBMCs co-cultured with IL-15 with or without JEG-3 for
six days resulted in an increase in the CD56brightCD16- NK cell
subpopulation and a reduction in the CD56dimCD16+ NK cell
subpopulation. Interleukin-15 and the JEG-3 cells seemed to some
degree to have an additive effect. Additionally, we observed an
increase in the KIR2DL4 and ILT2 receptors on the CD56brightCD16-
NK cell subpopulation after co-culture with IL-15 and JEG-3 cells.
Conclusion: Our main findings were an increase in the
CD56brightCD16- NK cell subpopulation after co-cultures with
PBMCs and the trophoblast-derived choriocarcinoma cell line JEG-
3 and addition of IL-15. The effect was primarily driven by IL-15.
The results may indicate that the cytokine IL-15 and trophoblast cells
at the fetalmaternal interface induce an increase in the
CD56brightCD16- NK cell subpopulation of importance for fetalma-
ternal immune interactions and placentation