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Binding of the placental growth factor to VEGF receptor type 1 modulates human T cell functions
Author(s) -
Leplina Olga,
Smetanenko Ekaterina,
Tikhonova Marina,
Batorov Egor,
Tyrinova Tamara,
Pasman Natalya,
Ostanin Alexander,
Chernykh Elena
Publication year - 2020
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.2a0420-723rr
Subject(s) - biology , cd8 , cytotoxic t cell , t cell , cd3 , microbiology and biotechnology , antigen , immunology , immune system , in vitro , biochemistry
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 ( 3 H‐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.