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

Li Wang, Rotem Rubinstein, Janet L. Lines, Anna Wasiuk, Cory Ahonen, Yanxia Guo, Li Fan Lu, David Gondek, Yan Wang, Roy A. Fava, Andras Fiser, Steve Almo, Randolph J. Noelle

Research output: Contribution to journalArticle

223 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)577-592
Number of pages16
JournalJournal of Experimental Medicine
Volume208
Issue number3
DOIs
StatePublished - Mar 14 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Wang, L., Rubinstein, R., Lines, J. L., Wasiuk, A., Ahonen, C., Guo, Y., Lu, L. F., Gondek, D., Wang, Y., Fava, R. A., Fiser, A., Almo, S., & Noelle, R. J. (2011). VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses. Journal of Experimental Medicine, 208(3), 577-592. https://doi.org/10.1084/jem.20100619