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2018 Abstracts

Modeling Decidual NK cell transfer of Granulysin to Trophoblast Cells using stimulated Peripheral Blood NK cells

Kayleigh Ingersoll, Brigham Young University

Natural killer (NK) cells are the most abundant immune cell type in the human first trimester placental interface (over 70%). Named decidual natural killer cells (dNK), they must protect the maternal-fetal interface from infection while maintaining tolerance to the semi-allogeneic fetus. dNK are less cytotoxic than peripheral blood NK cells (pNK), even though they express high levels of cytotoxic granules, particularly granulysin (GNLY), which is expressed at higher levels in dNK than pNK. GNLY is a pore-forming antimicrobial peptide produced by cytotoxic lymphocytes (CD8+ T cells and NK cells)4. It selectively permeabilizes bacterial and parasitic membranes, allowing granzymes (serine proteases) to enter and trigger oxidative microbial programmed cell death. While bacterial killing usually involves killing the infected cell, dNK and pNK are able to kill intracellular bacteria in primary trophoblast (placental cells) and trophoblast cell lines (JEG-3) without killing the host cells. The killing mechanism is dependent on transfer of granulysin from NK cells to trophoblasts, without degranulation of granzymes and perforin. The transfer may occur through direct contact between NK and JEG-3 by cytoplasmic projections, or by constitutive secretion of GNLY by dNK and uptake by JEG-3, which occurs by clathrin-mediated endocytosis. While GNLY is detected in JEG-3 (by fluorescent staining and flow cytometry) after co-culture with freshly isolated dNK, the levels of GNLY transferred to JEG-3 by freshly isolated pNK are too low for detection, albeit sufficient to kill bacteria. I waned to know whether pNK also transfer GNLY to trophoblasts like dNK and the mechanism responsible for transfer. To address this question, I activated pNK to increase their expression of GNLY to levels that would allow me to detect GNLY transfer to JEG-3.