Фактор роста плаценты модулирует ответ активированных in vitro T-клеток

Translated title of the contribution: Placental growth factor exerts modulatory effects on in vitro activated T cells

A. Smetanenko Ekaterina, Y. Leplina Olga, A. Tikhonova Marina, M. Pasman Natalia, A. Ostanin Alexander, R. Chernykh Elena

Research output: Contribution to journalArticlepeer-review

Abstract

Background. Recent studies demonstrated immunosuppressive properties of vascular endothelial growth factor (VEGF-A) and identified VEGF-A as a key mediator of tumor-induced immunosuppression. Placental growth factor (PlGF) is another member of VEGF family in which dramatic elevation is associated with effective immune adaptation in successful pregnancy, whereas low concentrations are related to pregnancy complications resulting from the activation of immune system. Previously, we have shown that activated T cells express VEGF receptor type 1 (VEGFR-1), and PlGF inhibits T cell proliferation in VEGFR-1-dependent manner. The aim of the present study was to further characterize PlGF effects on T cell responses in vitro. Materials and methods. Peripheral blood mononuclear cells (PBMC) from healthy donors were stimulated with anti-CD3 monoclonal antibodies (a-CD3) in the absence or presence of PlGF and assessed for IL-10 production, programmed cell death and the expression of inhibitory receptors (PD-1, CTLA-4, Tim-3) in CD4+ and CD8+ T cell subsets. Results. The addition of PlGF to PBMC cultures activated with a-CD3 resulted in increased percentages of IL- 10-producing CD4+ and CD8+ T cells. Besides, PlGF promoted CD8+ T cells apoptosis while did not affect programmed cell death within CD4+ T cells. Notable, T cell activation with a-CD3 in the presence of PlGF was accompanied by the enhancement of PD-1-expressing cells in CD8+ T cell subset and Tim-3-expressing cells in both CD4+ and CD8+ T cells, and by the increased expression of PD-1 and Tim-3 on T cells. Conclusion. Our in vitro findings indicate that PlGF can inhibit T cell responses due to the increasing interleukin-10 (IL-10) production, promoting CD8+ T cell apoptosis and enhancing the expression of PD-1 and Tim-3 inhibitory receptors. Given the elevated levels of PlGF in successful pregnancy and its decrease in gestation complications, the obtained data also suggest that PlGF-mediated suppression may be implicated into the governing immune evasion in pregnancy.

Translated title of the contributionPlacental growth factor exerts modulatory effects on in vitro activated T cells
Original languageRussian
Article number21
Pages (from-to)158-166
Number of pages9
JournalBulletin of Siberian Medicine
Volume19
Issue number4
DOIs
Publication statusPublished - Jan 2020

Keywords

  • Apoptosis
  • CTLA-4
  • IL-10
  • Inhibitory receptors
  • PD-1
  • PlGF
  • T cells
  • Tim-3

State classification of scientific and technological information

  • 76 MEDICINE AND HEALTH CARE

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