Glucocorticoids are anti inflammatory and immunosuppressive agents with pleiotropic effects on the growth, differentiation, and functional activity of T lymphocytes. The comprehensive assessment of the influence of dexamethasone on the functional activity of T cells with different grades of differentiation was performed under experimental in vitro conditions. We established that dexamethasone suppressed the func tional activity of CD45RA + and CD45RO + T lymphocytes. In the population of naive (CD45RA + ) T cells, the inhibitory effect of dexamethasone on the early activation stages (IL 2 dependent, associated with the CD25 expression and IL 2 production) was more significant, whereas in the culture of primed memory cells (CD45RO + ), dexamethasone affects the later stages (IL 2 independent, associated with the expression of proliferation molecule CD71). Multidirectional effects of dexamethasone on the level of expression of mRNA of telomerase catalytic unit (hTERT) were associated with the degree of T cells differentiation. Most likely, the role of glucocorticoid hormones in immunogenesis is mainly the suppression of the excessive growth of T cells and the maintenance of the clonal balance in lymphoid tissue. CELL MOLECULAR BIOLOGYAbbreviations: Ac/Exp, T Cell Activation/Expansion Kit human; CD, cluster of differentiation; IL 2, interleukin 2; IL 2R, interleu kin 2 receptor; hTERT, human telomerase reverse transcriptase.

The role of pregnancy-specific β1-glycoprotein (PSG) in the regulation of molecular genetic factors determining the functional activity of naїve T cells and T cells of immune memoryin vitrowas studied. Human PSG was isolated with a proprietary immuno-purification method using a biospecific sorbent followed by removing of immunoglobulin contamination with a HiTrapTMProtein G HP column. Physiological concentrations of PSG were used in the experiments. They corresponded to PSG levels in the peripheral blood of pregnant woman: 1, 10 and 100 μg/ml (I, II, III trimester, respectively). The objects of study were monocultures of naїve T cells (CD45RA+) and memory T cells (CD45R0+), obtained by immunomagnetic separation from the peripheral blood of women of reproductive age.It was established that at the level of naїve T cells (CD45RA+) PSG inhibited the expression of CD28 (1, 10, 100 μg/ml) and CD25 (100 μg/ml), without affecting the interleukin-2 (IL-2) production by these cells. At the same time, PSG in all concentrations studied suppressed the expression of CD25 at the immune memory T-cell (CD45R0+) surface but increased the IL-2 production. Expression ofU2af1l4, Gfi1, hnRNPLLgenes regulating the alternative splicing of the Ptprc gene encoding CD45 was also evaluated. It was found, that PSG reduced the expression of theGfi1(1, 10, 100 μg/ml),hnRNPLL(10, 100 μg/ml) genes, but increased the expression of theU2af1l4gene (1, 10, 100 μg/ml) in the naїve T cells. It was shown that at the immune memory T-cells’ level the effects were similar, with PSG rendering them in all concentrations used. The revealed changes in the mRNA transcription ofU2af1l4,Gfi1andhnRNPLLgenes in the studied T cell subsets may lead to the inhibition of CD45 “mature” isoform formation – CD45R0.Thus, PSG reduces the functional activity of naїve T cells and immune memory T cells associated with the expression of costimulation/activation molecules CD25 and CD28 and is involved in the regulation ofPtprcgene alternative splicing, which determines the ratio of CD45 molecule variants. Apparently, using these mechanisms, PSG regulates the functional activity of the memory T cell circulating pool, which is potentially capable of carrying out antigen-specific cytotoxic reactions against fetal antigens in vivo. In general, the data obtained broadens the notion of the PSG role in the regulation of molecular-genetic mechanisms of naїve T cells and immune memory T cells differentiation.

Природа микроокружения и его взаимодействие со стволовыми клетками являются одним из фундаментальных вопросов биологии и медицины [1]. Большие надежды возлагаются на использование клеточных технологий и тканевой инженерии для коррекции заболеваний в карди-УДК 602.6/.9

Адрес для переписки:Литвинова Лариса Сергеевна ФГАОУ ВО «Балтийский федеральный университет имени И. Канта» 236016, Россия, г. Калининград, ул. Боткина, 3. Тел.: 8 (4012) 59-55-95 (доб. 6631). E-mail: larisalitvinova@yandex.ru Address for correspondence : Litvinova Larisa S. Immanuel Kant Baltic Federal University 236016, Russian Federation, Kaliningrad, Botkina str., 3. Phone: 7 (4012) 59-55-95 (acc. 6631 Т-лимфоцитов in vitro» // Медицинская иммунология, 2018. Т. 20, № 1. С. 45-52. doi: 10.15789/1563-0625-2018-1-45-52 © Юрова К.А. и соавт., 2018 For citation: K.A. Yurova, O.G. Khaziakhmatova, N.M. Todosenko, upon in vitro maturation and differentiation of CD4 + CD45RО + / CD8 + CD45RО + T cells", Medical Immunology (Russia)/ Meditsinskaya Immunologiya, 2018, Vol. 20, no. 1, pp. 45-52. doi: 10.15789/1563-0625-2018 Резюме. Исследовано влияние γс-цитокинов (IL-2, IL-7 и IL-15) на созревание и дифференциров-ку цитотоксических и хелперных популяций CD45RО + Т-клеток в условиях гомеостатического куль-тивирования in vitro. Выявлено, что IL-2, IL-7 и IL-15 опосредуют созревание и дифференцировку CD8 + Т-лимфоцитов центральной памяти, пополняя популяцию клеток, обладающих эффекторными функциями. Действие IL-2 на CD4 + Т-клетки центральной памяти сопровождается генерацией клеток эффекторной памяти за счет снижения числа незрелых эффекторов -CD62L -CD27 + , тогда как IL-7 стимулирует образование незрелых эффекторов -CD62L -CD27 + . В субпопуляции CD8 + CD45RО + лимфоцитов IL-2, IL-7 и IL-15 инициируют образование терминально-дифференцированных клеток, обеспечивающих устойчивую иммунологическую память на реинвазию патогена. Immanuel Kant Baltic Federal University, Kaliningrad, Russian FederationAbstract. Effect of γс-cytokines (IL-2, IL-7 и IL-15) upon maturation and differentiation of cytotoxic and helper CD45RО + T cell population was studied in the homeostatic in vitro culture conditions. We have found that IL-2, IL-7 and IL-15 mediate maturation and differentiation of CD8 T cells central memory, replenishing the population of cells that exhibit effector functions. Action of IL-2 on CD4 + central memory T cells is accociated with generation of effector memory cells by reducing the number of immature effectors (CD62L -CD27 + ), whereas IL-7 promotes the formation of immature (CD62L -CD27 + ) effectors. IL-2, IL-7 and IL-15 initiate formation of terminally-differentiated cells in a subpopulation of CD8 + CD45RO + lymphocytes, providing a stable immunological memory to a pathogen reinfestation.

Molecular genetic mechanisms, signaling pathways, cultural conditions, factors, and markers of osteogenic differentiation of mesenchymal stem cells (MSC) are actively studied despite numerous works in this area of cellular technologies. This is largely due to the accumulating contradictions in seemingly classical knowledge, as well as permanent updating of the results in the field. In this regard, we focused on the main classical concepts and some new factors and mechanisms that have a noticeable regulatory effect on the differentiation potential of postnatal MSCs. The present review considers the significance of MSC sources for their differentiation capacity, as well as the role of the cellular microenvironment. The issues of classification, terminology, and functional activity of MSCs from various sources are discussed. The paracrine potential of MSCs in tissue regeneration has been considered; sufficient importance of inflammation in osteogenesis is noted, in particular, the presence of inflammatory cytokines and chemokines in the lesion focus, produced not only by microenvironmental cells but also by blood cells, including mononuclear leukocytes, migrating to the affected site. An important role in this review is given to biomechanical signals and to influence of conformational changes in cell cytoskeleton (cell shape) upon MSC differentiation, since the morphological features of cells and the structure of cytoskeleton are modulated by interactions of the cell surface with environmental factors, including hydrostatic pressure, fluid flow, compression/stretching loads. The data are presented concerning elasticity of extracellular matrix being a determining factor of cell differentiation. We conclude that one should switch from point studies of individual gene effects to multiple measurements of the gene-regulatory profile and biomolecules responsible for multiple, still poorly studied osteogenic factors of endogenous and exogenous origin. Among cornerstones in future (epi)genetic studies will be to decide if osteomodulatory effects are realized through specific signaling pathways and/or via cross-signaling with known genes controlling osteogenic differentiation of MSCs.