DataSheet_1_Ligand-Receptor Interactions of Galectin-9 and VISTA Suppress Human T Lymphocyte Cytotoxic Activity.docx (1.04 MB)
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DataSheet_1_Ligand-Receptor Interactions of Galectin-9 and VISTA Suppress Human T Lymphocyte Cytotoxic Activity.docx

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posted on 20.11.2020, 05:10 by 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, Elizaveta Fasler-Kan, Vadim V. Sumbayev

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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