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 A. Casely‐Hayford, Walter Fiedler, Jasmin Wellbrock, Cloé Desmet, Luigi Calzolai, Luca Varani, Steffen Berger, Ulrike Raap, Bernhard F. Gibbs, Elizaveta Fasler‐Kan, Vadim V. Sumbayev
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.