Abstract
During pregnancy, uterine NK cells interact with trophoblast cells. In addition to contact interactions, uterine NK cells are influenced by cytokines, which are secreted by the cells of the decidua microenvironment. Cytokines can affect the phenotypic characteristics of NK cells and change their functional activity. An imbalance of pro- and anti-inflammatory signals can lead to the development of reproductive pathology. The aim of this study was to assess the effects of cytokines on NK cells in the presence of trophoblast cells in an in vitro model. We used TNFα, IFNγ, TGFβ and IL-10; the NK-92 cell line; and peripheral blood NK cells (pNKs) from healthy, non-pregnant women. For trophoblast cells, the JEG-3 cell line was used. In the monoculture of NK-92 cells, TNFα caused a decrease in CD56 expression. In the coculture of NK cells with JEG-3 cells, TNFα increased the expression of NKG2C and NKG2A by NK-92 cells. Under the influence of TGFβ, the expression of CD56 increased and the expression of NKp30 decreased in the monoculture. After the preliminary cultivation of NK-92 cells in the presence of TGFβ, their cytotoxicity increased. In the case of adding TGFβ to the PBMC culture, as well as coculturing PBMCs and JEG-3 cells, the expression of CD56 and NKp44 by pNK cells was reduced. The differences in the effects of TGFβ in the model using NK-92 cells and pNK cells may be associated with the possible influence of monocytes or other lymphoid cells from the mononuclear fraction.
Highlights
Natural killer cells (NK cells) are cytotoxic, innate immunity lymphocytes that are characterized by the presence of the surface receptors CD45 and CD56, as well as the absence of the linear differentiation receptors CD3, CD14 and CD19 [1]
The addition of TNFα resulted in a decrease in the expression of the CD56 receptor by NK-92 cells compared to cultivation without TNFα in both IL-2+ and IL-2-free media (Figure 2a)
TNFα caused a decrease in CD56 expression by NK-92 cells and stimulated their cytotoxic function
Summary
Natural killer cells (NK cells) are cytotoxic, innate immunity lymphocytes that are characterized by the presence of the surface receptors CD45 and CD56, as well as the absence of the linear differentiation receptors CD3, CD14 and CD19 [1]. Fewer NK cells reside in the endometrium in non-pregnant women [4]
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