IL-18 is present at the maternal-fetal interface and enhances cytotoxic activity of decidual lymphocytes.
OBJECTIVE
Perforin expressing uterine natural killer (uNK) cells are under complex cytokine influence. The aim of the study was to investigate the presence and role of interleukin (IL)-18 on NK cytolytic potential at maternal-fetal (M-F) interface.


METHODS
Peripheral blood cells and decidual tissue were obtained from elective pregnancy termination of normal human 6-10-week-old pregnancies. Perforin expression and cytolytic activity of peripheral blood (PBL) and decidual lymphocytes (DL) were analyzed by flow cytometry. IL-18 positive decidual adherent cells (DAC) were detected by the same method. Interleukin-18 and IL-18 receptor (IL-18R) expression on the trophoblastic cells was detected by immunohistology using biotinylated anti-IL-18 and IL-18R monoclonal antibodies.


RESULTS
The IL-18 added in a dose of 10 ng/mL up-regulates perforin expression and cytolytic activity of DL. Simultaneous stimulation with IL-18 and IL-12 enhanced DL cytolytic activity, while IL-18 combined with IL-10 or IL-15 did not show this effect. Cytolytic activity of PBL was up-regulated by IL-18 as well, and this effect was enhanced by the addition of IL-12 and IL-15. Interleukin-18 did not affect perforin-protein expression in cultured PBL. Approximately 20% of DAC were IL-18 positive and these cells were mostly human leukocyte antigen (HLA)-DR negative. IL-18R positive cells were found on syncytiotrophoblast cell layer, interstitial tissue cells of villi and fetal blood cells. There was no detectable IL-18 staining on trophoblast cell layer on villi, but strong staining of fetal blood cells in villous vessels.


CONCLUSIONS
These are first results showing IL-18R expression, but not IL-18 expression on villous trophoblastic cells, as well as enhancement of perforin expression and NK cytolytic potential of DL under the influence of IL-18. IL-18 in concert with other cytokines and hormones could play an important role in the regulation of cytolytic potential of first trimester pregnancy decidual and peripheral blood NK cells.
Tokmadzić
Vlatka S
VS
Department of Physiology and Immunology, Medical Faculty, University of Rijeka, Rijeka, Croatia.
Tsuji
Yoshiyuki
Y
Bogović
Tatjana
T
Laskarin
Gordana
G
Cupurdija
Kristijan
K
Strbo
Natasa
N
Koyama
Koji
K
Okamura
Haruki
H
Podack
Eckhard R
ER
Rukavina
Daniel
D
D000328:Adult; D002824:Chorionic Villi / Q000378:metabolism; D003656:Decidua / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D020382:Interleukin-18 / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011247:Pregnancy
D020382:Interleukin-18; D007378:Interleukins; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin