VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses

L Wang, R Rubinstein, JL Lines, A Wasiuk… - Journal of Experimental …, 2011 - rupress.org
L Wang, R Rubinstein, JL Lines, A Wasiuk, C Ahonen, Y Guo, LF Lu, D Gondek, Y Wang…
Journal of Experimental Medicine, 2011rupress.org
The immunoglobulin (Ig) superfamily consists of many critical immune regulators, including
the B7 family ligands and receptors. In this study, we identify a novel and structurally distinct
Ig superfamily inhibitory ligand, whose extracellular domain bears homology to the B7 family
ligand PD-L1. This molecule is designated V-domain Ig suppressor of T cell activation
(VISTA). VISTA is primarily expressed on hematopoietic cells, and VISTA expression is
highly regulated on myeloid antigen-presenting cells (APCs) and T cells. A soluble VISTA-Ig …
The immunoglobulin (Ig) superfamily consists of many critical immune regulators, including the B7 family ligands and receptors. In this study, we identify a novel and structurally distinct Ig superfamily inhibitory ligand, whose extracellular domain bears homology to the B7 family ligand PD-L1. This molecule is designated V-domain Ig suppressor of T cell activation (VISTA). VISTA is primarily expressed on hematopoietic cells, and VISTA expression is highly regulated on myeloid antigen-presenting cells (APCs) and T cells. A soluble VISTA-Ig fusion protein or VISTA expression on APCs inhibits T cell proliferation and cytokine production in vitro. A VISTA-specific monoclonal antibody interferes with VISTA-induced suppression of T cell responses by VISTA-expressing APCs in vitro. Furthermore, anti-VISTA treatment exacerbates the development of the T cell–mediated autoimmune disease experimental autoimmune encephalomyelitis in mice. Finally, VISTA overexpression on tumor cells interferes with protective antitumor immunity in vivo in mice. These findings show that VISTA, a novel immunoregulatory molecule, has functional activities that are nonredundant with other Ig superfamily members and may play a role in the development of autoimmunity and immune surveillance in cancer.
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