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- Title
Ligand-Receptor Interactions of Galectin-9 and VISTA Suppress Human T Lymphocyte Cytotoxic Activity.
- Authors
Yasinska, Inna M.; Meyer, N. Helge; Schlichtner, Stephanie; Hussain, Rohanah; Siligardi, Giuliano; Casely-Hayford, Maxwell; Fiedler, Walter; Wellbrock, Jasmin; Desmet, Cloe; Calzolai, Luigi; Varani, Luca; Berger, Steffen M.; Raap, Ulrike; Gibbs, Bernhard F.; Fasler-Kan, Elizaveta; Sumbayev, Vadim V.
- 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.
- Subjects
CYTOTOXIC T cells; BONE marrow cancer; SUPPRESSOR cells; ACUTE myeloid leukemia; T cells
- Publication
Frontiers in Immunology, 2020, Vol 11, pN.PAG
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2020.580557