NK-клетки представляют собой лимфоциты, способные к контактному цитолизу вирус- инфицированных клеток и опухолевых клеток и являющиеся источником цитокинов, стимулирующих другие клетки иммунной системы и способствующих развитию иммунного ответа. Дифференцировка NK-клеток связана с последовательным приобретением стволовыми клетками специфичных для NK-клеток рецепторов и становлением функциональных характеристик натуральных киллеров. Целью настоящего обзора было рассмотрение CD56dim и CD56bright популяций NK-клеток в процессе их дифференцировки. В обзоре описаны поверхностные рецепторы NK-клеток и экспрессия ими транскрипционных факторов на разных стадиях дифференцировки, представлена сравнительная характеристика данных о влиянии цитокинов и клеток микроокружения на процесс дифференцировки NK-клеток, рассмотрено явление существования NK-клеток, подобных клеткам памяти. Особый интерес представляет дифференцировка NK-клеток матки, так как эти клетки являются особой популяцией NK-клеток, которая преобладает среди лимфоцитов децидуальной оболочки при беременности и принимает участие в процессе образования и ремоделирования плаценты. В обзоре рассмотрены особенности дифференцировки NK-клеток матки, учитывая возможность образования этой популяции NK-клеток как из NK-клеток периферической крови, так и пролиферации in situ. Изучение особенностей функционального состояния NK-клеток матки позволит в дальнейшем приблизиться к пониманию роли NK-клеток при беременности и нарушению оказываемой NK-клетками регуляции в зоне маточно-плацентарного контакта при патологии беременности.

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.

Natural killer (NK) cells are of special interest among a multitude of microvesicle (MV) source cells. NK cells are a lymphocyte subpopulation performing contact cytolysis of virus-infected cells and tumor cells. Each of the NK cell populations has a unique receptor repertoire on its surface and, thus, unique functions. During their contact with a target cell, the most common mechanism of cytolysis is an exocytosis of lytic granules. However, some indirect evidence suggests that MV with CD56 phenotype and leukocyte-derived MV with various phenotypes are present in the peripheral blood plasma.This research is aimed to study the phenotype, composition and cytotoxic activity of microvesicles produced by NK cells. The analysis of receptor expression showed that MV, as well as source cells of the NK-92 cell line, had a similar CD56 molecule expression profile. The expression profile in MV differs from the same in source cells by higher CD119 and CD11b expression and by lower CD18 expression. Culturing of NK-92 cells in the presence of PMA, IL-1β, TNFα, IFNγ resulted in alterations of cell phenotypes and MV. Immunoblots revealed a change of perforin and granzyme B (GrB) in MV. The analysis of the cytotoxic activity of NK-92 cells in a natural killer in vitro assay employing K562 target cells demonstrated that MV obtained from TNFα-activated cells of the NK-92 cell line increased the cytotoxicity of the same TNFα-activated NK-92 cells regarding cytotoxicity levels. This coincides with the previously revealed increased content of GrB in MV obtained from TNFα-activated cells of the NK-92 cell line. To sum up depending on the cytokine NK-92 cells produce MV that differ in their phenotype, composition and activity. Any changes in MV composition can result in changes in their functional activity: in particular, changes can increase the cytotoxic activity of NK cells of the NK-92 cell line. Thus, besides a well-known and proved way for GrB delivery to a target cell, we can suggest an additional way – the transportation of GrB within MV.