Immunoregulatory potential of pregnancy-specific β1-glycoprotein

Abstract

The embryo, being half an antigenically “foreign” organism, should elicit a maternal immune response. During evolution, however, the mechanisms ensuring successful development of pregnancy have been formed. In particular, among factors providing immune tolerance during pregnancy are some proteins associated with pregnancy. The pregnancy-specific β 1-glycoprotein (PSG, PSG1; SP1; PSβG1) is a dominant fetoplacental protein produced by cyto- and syncytiotrophoblast cells, and it exhibits immunosuppressive properties. Our team of authors possesses a patented method for obtaining native human PSG preparation from blood serum of pregnant women, a mixture of PSG1, PSG3, PSG7, PSG9, and their isoforms and precursors. This review presents an analysis of our results for the period from 2015 to 2020. We studied the immunoregu-latory effects of the obtained PSG preparation at concentrations comparable to those observed in pregnancy (1, 10, 100 |ag/mL). The study was performed with peripheral blood cells obtained from non-pregnant women. It was found that PSG significantly increased the percentage of adaptive Tregs in vitro, as well as expression of CTLA-4, GITR, and production of IL-10 by these cells. It has been shown that PSG has a stimulating effect upon indoleamine-2,3-dioxygenase (IDO) activity of peripheral blood monocytes. For Th17 cells, we have demonstrated that PSG can suppress differentiation and proliferation of these cells, along with reduced production of critical proinflammatory cytokines (IL-8, IL-10, IL-17, IFNγ, MCP-1, TNF α). As for the memory T cells, PSG suppressed CD25 expression and IL-2 production by them, along with simultaneous decreased expression of Gfi1, hnRNPLL genes, thus preventing the formation of the “mature” CD45R0 isoform. PSG has been shown to inhibit naive T cells’ conversion to the terminally differentiated effector subpopulation of helper T cells. When analyzing PSG effects upon cytokine profile of immunocompetent cells, it was found that the protein predominantly suppresses the Th1 cytokine production by the studied cell types, and regulates the Th2 cytokine production in divergent manner. The results obtained are consistent with general concept of immunosuppression during pregnancy. Thus, PSG could be one of the factors preventing formation and implementation of immune response to placental antigens.

Effect of Pregnancy Specific β1-Glycoprotein on the Replicative Potential of Naïve T Cells and Immune Memory T Cells

“…Human PSG was obtained using the authors' patented method of immunopurification with the biospecific sorbent and subsequent cleaning from the immunoglobulin contamination with HiTrap Protein G HP column (Amersham Biosciences) [1]. Physiological concentrations of PSG corresponding to maternal peripheral blood concentrations during pregnancy, namely 1, 10, and 100 µg/ml (first, second, and third trimester, respectively) [3], were used in experiments.…”

“…Pregnancy-specific β1-glycoprotein (PSG) is a predominant fetoplacental protein produced by cyto-and syncytiotrophoblast cells and possesses various immunoregulatory effects [3]. We have earlier demonstrated that native PSG preparation could regulate the molecular-genetic factors governing the differentiation of immune memory T cells.…”

Effect of pregnancy-specific β1-glycoprotein on the expression of arginase-1 and indolamine-2,3-dioxygenase by myeloid-derived suppressor cells

“…PSG) является доминирующим фетоплацентарным белком, обладающим иммуномодулирующими свойствами. За последние 10 лет, благодаря разработке авторского метода получения нативного препарата ТБГ человека [1], мы продемонстрировали эффекты этого белка в отношении различных популяций иммунных клеток [10]. Было установлено, что ТБГ стимулирует экспрессию IDO моноцитами женщин, подавляет пролиферацию и дифференцировку Th17, подавляет продукцию провоспалительных цитокинов (IL-8, IL-17, IFNγ, MCP-1, TNFα) а также G-CSF и GM-CSF [10].…”

“…За последние 10 лет, благодаря разработке авторского метода получения нативного препарата ТБГ человека [1], мы продемонстрировали эффекты этого белка в отношении различных популяций иммунных клеток [10]. Было установлено, что ТБГ стимулирует экспрессию IDO моноцитами женщин, подавляет пролиферацию и дифференцировку Th17, подавляет продукцию провоспалительных цитокинов (IL-8, IL-17, IFNγ, MCP-1, TNFα) а также G-CSF и GM-CSF [10]. Помимо этого, было установлено, что ТБГ угнетал экспрессию маркеров активации CD28 и CD25 наивными Т-клетками, не влияя на продукцию ими IL-2, однако на уровне Т-клеток иммунной памяти ТБГ снижал поверхностную экспрессию CD25 одновременно со снижением продукции IL-2.…”