VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses. J Exp Med 2011 Mar 14;208(3):577-92
Date
03/09/2011Pubmed ID
21383057Pubmed Central ID
PMC3058578DOI
10.1084/jem.20100619Scopus ID
2-s2.0-79952717517 (requires institutional sign-in at Scopus site) 601 CitationsAbstract
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 List
Wang L, Rubinstein R, Lines JL, Wasiuk A, Ahonen C, Guo Y, Lu LF, Gondek D, Wang Y, Fava RA, Fiser A, Almo S, Noelle RJMESH terms used to index this publication - Major topics in bold
AnimalsAntibodies, Monoclonal
Antigen-Presenting Cells
B7 Antigens
B7-1 Antigen
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Encephalomyelitis, Autoimmune, Experimental
Flow Cytometry
Gene Expression Regulation
Immunoglobulins
Ligands
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Mice, Transgenic
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocytes
Tumor Cells, Cultured
