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

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). 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. 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. 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