Effect of Alpha-Fetoprotein on Differentiation of Myeloid Supressor Cells

Doklady Biochemistry and Biophysics - The effect of recombinant alpha-fetoprotein (AFP) on human myeloid suppressor cell (MDSC) differentiation was studied in vitro in the presence of cytokines...     

α-Fetoprotein Influence on the Conversion of Naïve T-Helpers into Memory T-Cell Effector Subpopulations

The effect of native α-fetoprotein (AFP) on the conversion of naïve T-helpers into central memory T-cells (TCM) and effector subpopulations of the preterminally differentiated (TEM) and terminally differentiated (TEMRA) memory T-cells was studied. AFP was found to prevent the conversion of naïve T-helpers into effector subpopulations of memory T cells (TEM and TEMRA) while reducing the total production of IL-4 and IFN-γ by the studied cell populations. The data reveal a new role of AFP in the immune tolerance formation during pregnancy.     

Role of α-fetoprotein in differentiation of regulatory T lymphocytes

The effect of native α-fetoprotein (AFP) on the expression of T-regulatory lymphocyte (Treg) markers by activated CD4⁺ lymphocytes with different proliferative status was studied. α-Fetoprotein did not affect the ratio of proliferating and non-proliferating activated CD4⁺ cells. In the study of Treg differentiation, it was found that AFP at concentrations of 50 and 100 μg/mL significantly inhibited the number of nonproliferating CD4⁺FOXP3⁺ and CD4⁺FOXP3⁺HELIOS⁺ lymphocytes without affecting the expression of Treg markers by proliferating CD4⁺ lymphocytes.     

Effect of pregnancy-specific β1-glycoprotein on indoleamine-2,3-dioxygenase activity in human monocytes

The role of heterogenic human pregnancy-specific glycoprotein (PSG), obtained by the authors’ technology, in the regulation of the indoleamine-2,3-dioxygenase (IDO) activity in female blood monocytes has been studied in vitro. PSG stimulated IDO activity under the conditions of induction of the monocytes by interferon-γ. Upon the induction of cell proliferation by lipopolysaccharides, the stimulating effect was obtained only with 10 μg/mL of PSG. Enhanced IDO activity is probably a factor of peripheral immunological tolerance and antimicrobial protection against intracellular infections in the gestation period.     

Role of toll-like receptors in realization of human chorionic gonadotropin effects on monocyte functional activity

Human chorionic gonadotropin (hCG) is analyzed here as an endogenous ligand for type 4 Toll-like proteins (TLR4). It is demonstrated that hCG actively binds to TLR4 molecules on monocyte surfaces. Using flow cytometry it was revealed that in the presence of high hCG concentrations (100 and 1000 IU/mL) the level of CD14⁺TLR4⁺-positive cells was reliably lowered in the gate of monocytes on 1, 5, and 10 min of experiment. Inhibition assay was used to study the role of TLR4 molecules in realization of hCG effects on monocyte functional activity. Monoclonal antibodies against TLR4 and/or resveratrol that blocks TRIF/TRAF6 intracellular proteins involved in signal transduction to IRF3 and NF-κB, respectively were applied to block TLR4-dependent signal transduction. In addition, protein kinase A (PKA) engaged in signal transduction from LH-receptor was suppressed. It was revealed that the inhibitory effect of hCG on monocyte phagocytic activity was TLR4-dependent, whereas its effects on myeloperoxidase (MPOex) secretion and spontaneous oxidative monocyte activity were PKA-dependent. It was found that hormone effects on stimulated oxidative activity of monocytes and their production of interleukin (IL)-1 and IL-8 depended both on TLR4 availability and PKA activity. Thus, a novel mechanism of hormone-monocyte interactions has been revealed that is mediated by TLR4 molecules that serve as non-canonical hormone receptors in monocytes.