Short-term Cytolytic Mediators' Expression in Decidual Lymphocytes is Enhanced by Interleukin-15

Authors: Strbo, Natasa1; Laskarin, Gordana1; Crncic, Tatjana Bogovic1; Juretic Frankovic, Koraljka1; Bedenicki, Ivica1; Tokmadzic, Vlatka Sotosek1; Randic, Ljiljana2; Bouteiller, Philippe Le3; Tabiasco, Julie3; Podack, Eckhard R.4; Rukavina, Daniel1

Source: American Journal of Reproductive Immunology, Volume 55, Number 3, March 2006 , pp. 217-225(9)

Publisher: Blackwell Publishing

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Abstract:

Problem

We investigated whether decidual adherent cells (DAC) and interleukin (IL)-15, in comparison to interleukin (IL)-2 affect cytolytic potential of first trimester decidual lymphocytes (DL). Method of study

Decidual mononuclear cells were obtained by enzymatic digestion and density gradient centrifugation. Non-adherent DL were collected after 2-hr adherence and cultured for 18 or 72 hr with: IL-15 (0.5–5 ng/mL), IL-2 (100–1000 U/mL) or both of these cytokines, DAC (ratio 3:1 and 1:1) or DAC and anti-IL-15 antibody. Perforin, Fas ligand (FasL) and granzyme B were detected at mRNA level in indicated culture conditions. Cytolytic activity of DL against K-562, P815 and P815-Fas was measured by 2-hr PKH-26 cytotoxicity assay. The dynamics of perforin protein and mRNA expression were measured in DL after a contact with K-562 targets. Results

Interleukin-15 enhanced perforin, FasL and granzyme B transcription after 18-hr culture and prevented perforin protein downregulation, observed after DL culture. IL-2 had similar effects. DAC sustained perforin expression in DL and anti-IL-15 monoclonal antibody abrogated this effect. DAC increased cytotoxicity of DL against K-562 which was mediated by IL-15. Conclusion

Interleukin-15, probably produced by DAC, upregulates cytolytic mediators' expression and perforin-mediated cytotoxicity of DL, with equal efficiency as high concentrations of IL-2.

Keywords: Cytotoxicity; decidual NK cells; Fas ligand; interleukin-15; perforin

Document Type: Research article

DOI: 10.1111/j.1600-0897.2005.00351.x

Affiliations: 1: Department of Physiology and Immunology, Medical Faculty, University of Rijeka, Rijeka, Croatia; 2: Department of Obstetrics and Gynecology, Clinical Hospital University of Rijeka, Rijeka, Croatia; 3: INSERM U563, Hôpital Purpan, Toulouse, France; 4: Department of Microbiology and Immunology, School of Medicine, University of Miami, Miami, FL, USA

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