Regulation of natural killer cells cytotoxicity by trophoblast cells: proteins and receptors

Background: Interaction between trophoblast and natural killer cells is determined by microenvironment.Cytotoxicity of NK against targets, including trophoblasts, is associated with production of perforin, granzymes.Trophoblasts are not destroyed by NK but trophoblast-cell resistance is understudied.The aim of the study: To evaluate the interaction between NK and trophoblasts in the presence of cytokines typical of the uteroplacental contact microenvironment during pregnancy.We evaluated changes in the expression of proteins responsible for the implementation of cytotoxic function in NK and trophoblast cells under short-term and long-term coculture.Materials and methods: In this study we used cell cultures -NK-92 and JEG-3 as a model of interaction between fetus and mother's immune system.To analyze changes in phenotype, cytokines secretion and amount of cytotoxicity proteins we used flow cytometry.Results: We observed that intensity of GrA expression by NK-92 was lower than GrB.There was no transfer of GrA to trophoblast within 24 hours of co-culturing.The appearance of GrA in trophoblast with a simultaneous decrease in expression by NK-92 was noted after 96 hours.NK-92 and JEG-3 cells constitutively expressed serpin B9.Cytokines did not affect the content of GrA, GrB, perforin, and serpin B9 in the NK-92 monoculture.IL-15, IL-18, IL-10 caused a decrease in serpin B9 expression by trophoblasts, but co-culturing with NK-92 diminished this effect.When co-cultured with trophoblasts for 96 hours, intensity of expression of GrA, GrB, perforin and serpin B9 by NK-92 decreased.TNF and IL-15 decreased the inhibitory effect of trophoblasts on GrA expression by NK.IL-15 and TGF caused an increase in the number of JEG-3 containing GrA. Conclusion: The interaction between NK and trophoblasts is a dynamic process accompanied by the transfer of cytotoxic proteins and changes in the expression of serpin B9.The used cytokines affected the transfer of proapoptotic proteins in co-culture.