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, Steven C. Almo, Randolph J. Noelle

Research output: Contribution to journalArticle

188 Citations (Scopus)

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

Fingerprint

Immunoglobulins
Ligands
T-Lymphocytes
Antigen-Presenting Cells
Immunoglobulin Domains
CD27 Antigens
Immunoglobulin Variable Region
Autoimmune Experimental Encephalomyelitis
Myeloid Cells
Autoimmunity
Autoimmune Diseases
Immunity
Neoplasms
Monoclonal Antibodies
Cell Proliferation
Cytokines

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Wang, L., Rubinstein, R., Lines, J. L., Wasiuk, A., Ahonen, C., Guo, Y., ... 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

VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses. / Wang, Li; Rubinstein, Rotem; Lines, Janet L.; Wasiuk, Anna; Ahonen, Cory; Guo, Yanxia; Lu, Li Fan; Gondek, David; Wang, Yan; Fava, Roy A.; Fiser, Andras; Almo, Steven C.; Noelle, Randolph J.

In: Journal of Experimental Medicine, Vol. 208, No. 3, 14.03.2011, p. 577-592.

Research output: Contribution to journalArticle

Wang, L, Rubinstein, R, Lines, JL, Wasiuk, A, Ahonen, C, Guo, Y, Lu, LF, Gondek, D, Wang, Y, Fava, RA, Fiser, A, Almo, SC & Noelle, RJ 2011, 'VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses', Journal of Experimental Medicine, vol. 208, no. 3, pp. 577-592. https://doi.org/10.1084/jem.20100619
Wang, Li ; Rubinstein, Rotem ; Lines, Janet L. ; Wasiuk, Anna ; Ahonen, Cory ; Guo, Yanxia ; Lu, Li Fan ; Gondek, David ; Wang, Yan ; Fava, Roy A. ; Fiser, Andras ; Almo, Steven C. ; Noelle, Randolph J. / VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses. In: Journal of Experimental Medicine. 2011 ; Vol. 208, No. 3. pp. 577-592.
@article{964ec618963d47b88ded0c6f8677e288,
title = "VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses",
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.",
author = "Li Wang and Rotem Rubinstein and Lines, {Janet L.} and Anna Wasiuk and Cory Ahonen and Yanxia Guo and Lu, {Li Fan} and David Gondek and Yan Wang and Fava, {Roy A.} and Andras Fiser and Almo, {Steven C.} and Noelle, {Randolph J.}",
year = "2011",
month = "3",
day = "14",
doi = "10.1084/jem.20100619",
language = "English (US)",
volume = "208",
pages = "577--592",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "3",

}

TY - JOUR

T1 - VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses

AU - Wang, Li

AU - Rubinstein, Rotem

AU - Lines, Janet L.

AU - Wasiuk, Anna

AU - Ahonen, Cory

AU - Guo, Yanxia

AU - Lu, Li Fan

AU - Gondek, David

AU - Wang, Yan

AU - Fava, Roy A.

AU - Fiser, Andras

AU - Almo, Steven C.

AU - Noelle, Randolph J.

PY - 2011/3/14

Y1 - 2011/3/14

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79952717517&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952717517&partnerID=8YFLogxK

U2 - 10.1084/jem.20100619

DO - 10.1084/jem.20100619

M3 - Article

C2 - 21383057

AN - SCOPUS:79952717517

VL - 208

SP - 577

EP - 592

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 3

ER -