IL-18 is Present at the Maternal–Fetal Interface and Enhances Cytotoxic Activity of Decidual Lymphocytes
Article first published online: 5 SEP 2002
American Journal of Reproductive Immunology
Volume 48, Issue 4, pages 191–200, October 2002
How to Cite
TOKMADZ̆IĆ, V. S. , TSUJI, Y., BOGOVIĆ, T., LAŠKARIN, G., CUPURDIJA, K., Š TRBO , N., KOYAMA, K., OKAMURA, H., PODACK, E. R. and RUKAVINA, D. (2002), IL-18 is Present at the Maternal–Fetal Interface and Enhances Cytotoxic Activity of Decidual Lymphocytes. American Journal of Reproductive Immunology, 48: 191–200. doi: 10.1034/j.1600-0897.2002.01132.x
- Issue published online: 5 SEP 2002
- Article first published online: 5 SEP 2002
- IL-18 receptor;
- perforin-mediated cytotoxicity;
Tokmadz̆ić VS, Tsuji Y, Bogović T, Laškarin G, Cupurdija K, Štrbo N, Koyama K, Okamura H, Podack ER, Rukavina D. IL-18 is present at the maternal-fetal interface and enhances cytotoxic activity of decidual lymphocytes. AJRI 2002; 48:191–200 © Blackwell Munksgaard, 2002
PROBLEM: 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.
METHOD OF STUDY: 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.
CONCLUSION: 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.