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

• Published in: American journal of reproductive immunology (1989) 2006-03, Vol.55 (3), p.217-225
• Main Authors: Strbo, Natasa, Laskarin, Gordana, Crncic, Tatjana Bogovic, Juretic Frankovic, Koraljka, Bedenicki, Ivica, Tokmadzic, Vlatka Sotosek, Randic, Ljiljana, Bouteiller, Philippe Le, Tabiasco, Julie, Podack, Eckhard R., Rukavina, Daniel
• Format: Article
• Language: English
• Subjects: Adult; Cells, Cultured; Cytotoxicity; Decidua - cytology; Decidua - drug effects; Decidua - immunology; decidual NK cells; Fas ligand; Fas Ligand Protein; Female; Gene Expression Regulation - drug effects; Granzymes; Humans; interleukin-15; Interleukin-15 - immunology; Interleukin-15 - pharmacology; Interleukin-2 - immunology; Interleukin-2 - pharmacology; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Lymphocytes - drug effects; Lymphocytes - immunology; Membrane Glycoproteins - drug effects; Membrane Glycoproteins - genetics; Membrane Glycoproteins - immunology; Perforin; Pore Forming Cytotoxic Proteins; Reference Values; RNA, Messenger - drug effects; RNA, Messenger - immunology; Serine Endopeptidases - drug effects; Serine Endopeptidases - genetics; Serine Endopeptidases - immunology; Time Factors; Tumor Necrosis Factors - genetics; Tumor Necrosis Factors - immunology; Up-Regulation
• ISSN: 1046-7408; 1600-0897
• DOI: 10.1111/j.1600-0897.2005.00351.x

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.