Binding of the placental growth factor to VEGF receptor type 1 modulates human T cell functions

Olga Leplina, Ekaterina Smetanenko, Marina Tikhonova, Egor Batorov, Tamara Tyrinova, Natalya Pasman, Alexander Ostanin, Elena Chernykh

Результат исследования: Научные публикации в периодических изданияхстатья

Аннотация

The immunosuppressive properties of vascular endothelial growth factors (VEGFs) suggest a new role of angiogenic factors in T cell modulation in cancer and pregnancy. Most of VEGF effects on T cells are mediated through the VEGF receptor type 2 (VEGFR-2). This study aims to investigate the role of placental growth factor (PlGF) as a selective VEGFR-1 ligand in the modulation of human T cells functions. For this, PBMCs from healthy donors were stimulated with anti-CD3 mAbs (a-CD3) or Concanavalin A (ConA) in the absence or presence of PlGF and assessed for T cell proliferation, IL-10 production, programmed cell death, and the expression of inhibitory receptors (PD-1, CTLA-4, TIM-3) using radiometric (3H-thymidine incorporation) and FACS analysis. We showed that most T cells in freshly isolated PBMCs lacked VEGFR-1. However, activation with a-CD3 or ConA strongly increased the percentages of VEGFR-1 expressing CD4+ and CD8+ T cells. PlGF in a wide dose range suppressed PBMC cell proliferation, inhibiting both CD4+ and CD8+ T cells. Blockade of VEGFR-1, but not VEGFR-2 with neutralizing Abs completely abolished the suppressive effect of PlGF. Furthermore, we found that treatment with PlGF up-regulated IL-10 production in CD4+ and CD8+ T cells, promoted CD8+ T cells apoptosis and enhanced the expression of inhibitory receptors (PD-1 and TIM-3) on activated T cells. Our in vitro findings suggest the involvement of PlGF/VEGFR-1 signaling in the modulation of T cell responses in a-CD3-stimulated PBMCs.

Язык оригиналаанглийский
Страницы (с-по)1013-1024
Число страниц12
ЖурналJournal of Leukocyte Biology
Том108
Номер выпуска3
DOI
СостояниеОпубликовано - 1 сен 2020

Fingerprint Подробные сведения о темах исследования «Binding of the placental growth factor to VEGF receptor type 1 modulates human T cell functions». Вместе они формируют уникальный семантический отпечаток (fingerprint).

  • Цитировать

    Leplina, O., Smetanenko, E., Tikhonova, M., Batorov, E., Tyrinova, T., Pasman, N., Ostanin, A., & Chernykh, E. (2020). Binding of the placental growth factor to VEGF receptor type 1 modulates human T cell functions. Journal of Leukocyte Biology, 108(3), 1013-1024. https://doi.org/10.1002/JLB.2A0420-723RR