Frontiers in Immunology (Nov 2020)

Ligand-Receptor Interactions of Galectin-9 and VISTA Suppress Human T Lymphocyte Cytotoxic Activity

  • Inna M. Yasinska,
  • N. Helge Meyer,
  • Stephanie Schlichtner,
  • Rohanah Hussain,
  • Giuliano Siligardi,
  • Maxwell Casely-Hayford,
  • Walter Fiedler,
  • Jasmin Wellbrock,
  • Cloe Desmet,
  • Luigi Calzolai,
  • Luca Varani,
  • Steffen M. Berger,
  • Ulrike Raap,
  • Bernhard F. Gibbs,
  • Bernhard F. Gibbs,
  • Elizaveta Fasler-Kan,
  • Elizaveta Fasler-Kan,
  • Vadim V. Sumbayev

DOI
https://doi.org/10.3389/fimmu.2020.580557
Journal volume & issue
Vol. 11

Abstract

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Acute myeloid leukemia (AML), a blood/bone marrow cancer, is a severe and often fatal malignancy. AML cells are capable of impairing the anti-cancer activities of cytotoxic lymphoid cells. This includes the inactivation of natural killer (NK) cells and killing of T lymphocytes. Here we report for the first time that V-domain Ig-containing suppressor of T cell activation (VISTA), a protein expressed by T cells, recognizes galectin-9 secreted by AML cells as a ligand. Importantly, we found that soluble VISTA released by AML cells enhances the effect of galectin-9, most likely by forming multiprotein complexes on the surface of T cells and possibly creating a molecular barrier. These events cause changes in the plasma membrane potential of T cells leading to activation of granzyme B inside cytotoxic T cells, resulting in apoptosis.

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