Recombinant Cynomolgus VISTA/B7-H5 Fc Chimera (Catalog #9408-B7) inhibits anti-CD3antibody-induced IL-2 secretion in human T lymphocytes. The ED50 for this effect is 0.6-3 µg/mL.
V-domain Ig suppressor of T cell
activation (VISTA), also known as platelet receptor Gi24, Dies1, SISP1, PD-1H,
and B7‑H5, is a 45-55 kDa transmembrane glycoprotein with homology to B7-like
immune co-stimulatory molecules (1, 2). Mature cynomologus VISTA contains a
162 amino acid (aa) extracellular domain (ECD) with one V-type Ig-like
domain, a 21 aa transmembrane segment, and a 96 aa cytoplasmic
domain. Within the ECD, cynomologus VISTA shares 96% and 69% aa
sequence identity with human and mouse VISTA, respectively. The 30 kDa ECD
can be shed by MT1‑MMP, with a 25-30 kDa fragment remaining in the
membrane (3). VISTA promotes both MT1‑MMP expression and the MT1-MMP mediated
activation of MMP-2 (3). VISTA supports the differentiation of embryonic stem cells (ESC) and
enhances BMP4 induced signaling in ESC, but is also down regulated following
BMP4 exposure (4, 5). It binds to BMP4 directly, and also associates with the
type I BMP receptor Activin RIB/ALK 4 (4, 5). VISTA is highly expressed on
mature CD11b high myeloid-derived APCs and to a lesser extent on CD4+, CD8+,
and T regs and is also found on tumor infiltrating lymphocytes (7). It is up
regulated in vivo on activated monocytes and dendritic cells (5). VISTA
inhibits CD4+ and CD8+ T cell proliferation, and their production of IL2 and
IFN-gamma (6). Its expression on tumor cells attenuates the antitumor immune
response and enables more rapid tumor progression (6). In contrast, VISTA
limits disease progression in the autoimmune disease model EAE (6). VISTA-Ig suppressed proliferation of T cells but not
B cells and blunted the production of T cell cytokines and activation markers,
suggesting that VISTA as a negative checkpoint
regulator suppresses T cell activation (8, 9).
Flajnik, M.F. et al. (2012) Immunogenetics 64:571.
Wilcox, R.A. et al. (2012) Eur. J. Haematol. 88:465.
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