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

Yasinska, Inna M., Meyer, N. Helge, Schlichtner, Stephanie, Hussain, Rohanah, Siligardi, Giuliano, Casely-Hayford, Maxwell, Fiedler, Walter, Wellbrock, Jasmin, Desmet, Cloe, Calzolai, Luigi, and others. (2020) Ligand-Receptor Interactions of Galectin-9 and VISTA Suppress Human T Lymphocyte Cytotoxic Activity. Frontiers in Immunology, 11 . Article Number 580557. ISSN 1664-3224. (doi:10.3389/fimmu.2020.580557) (KAR id:84314)

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Official URL: https://doi.org/10.3389/fimmu.2020.580557

Abstract

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.

Item Type:	Article
DOI/Identification number:	10.3389/fimmu.2020.580557
Uncontrolled keywords:	Galectin-9, VISTA, T cells, NK cells, acute myeloid leukemia, immune escape
Divisions:	Divisions > Division of Natural Sciences > Medway School of Pharmacy
Depositing User:	Vadim Sumbayev
Date Deposited:	20 Nov 2020 16:32 UTC
Last Modified:	04 Mar 2024 18:45 UTC
Resource URI:	https://kar.kent.ac.uk/id/eprint/84314 (The current URI for this page, for reference purposes)

University of Kent Author Information

Gibbs, Bernhard F..

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Sumbayev, Vadim V..

Creator's ORCID:	https://orcid.org/0000-0002-9404-5626
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