Short-term cytolytic mediators' expression in decidual lymphocytes is enhanced by interleukin-15.
OBJECTIVE
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).


METHODS
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.


CONCLUSIONS
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.
Strbo
Natasa
N
Department of Physiology and Immunology, Medical Faculty, University of Rijeka, Rijeka, Croatia.
Laskarin
Gordana
G
Bogovic Crncic
Tatjana
T
Juretic Frankovic
Koraljka
K
Bedenicki
Ivica
I
Sotosek Tokmadzic
Vlatka
V
Randic
Ljiljana
L
Le Bouteiller
Philippe
P
Tabiasco
Julie
J
Podack
Eckhard R
ER
Rukavina
Daniel
D
D000328:Adult; D002478:Cells, Cultured; D003656:Decidua / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D053222:Fas Ligand Protein; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D053804:Granzymes; D006801:Humans; D019409:Interleukin-15 / Q000276:immunology / Q000494:pharmacology*; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger / Q000187:drug effects / Q000276:immunology; D012016:Reference Values; D012697:Serine Endopeptidases / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D013997:Time Factors; D048069:Tumor Necrosis Factors / Q000235:genetics* / Q000276:immunology; D015854:Up-Regulation
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D019409:Interleukin-15; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D048069:Tumor Necrosis Factors; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases