VSIG4, a B7 family–related protein, is a negative regulator of T cell activation
Lorenz Vogt, … , Philippe Saudan, Martin F. Bachmann
Lorenz Vogt, … , Philippe Saudan, Martin F. Bachmann
Published October 2, 2006
Citation Information: J Clin Invest. 2006;116(10):2817-2826. https://doi.org/10.1172/JCI25673.
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VSIG4, a B7 family–related protein, is a negative regulator of T cell activation

Abstract

T cell activation by APCs is positively and negatively regulated by members of the B7 family. We have identified a previously unknown function for B7 family–related protein V-set and Ig domain–containing 4 (VSIG4). In vitro experiments using VSIG4-Ig fusion molecules showed that VSIG4 is a strong negative regulator of murine and human T cell proliferation and IL-2 production. Administration to mice of soluble VSIG4-Ig fusion molecules reduced the induction of T cell responses in vivo and inhibited the production of Th cell–dependent IgG responses. Unlike that of B7 family members, surface expression of VSIG4 was restricted to resting tissue macrophages and absent upon activation by LPS or in autoimmune inflammatory foci. The specific expression of VSIG4 on resting macrophages in tissue suggests that this inhibitory ligand may be important for the maintenance of T cell unresponsiveness in healthy tissues.

Authors

Lorenz Vogt, Nicole Schmitz, Michael O. Kurrer, Monika Bauer, Heather I. Hinton, Silvia Behnke, Dominique Gatto, Peter Sebbel, Roger R. Beerli, Ivo Sonderegger, Manfred Kopf, Philippe Saudan, Martin F. Bachmann

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Figure 5

VSIG4 inhibits T cell proliferation and IL-2 production in vitro.

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VSIG4 inhibits T cell proliferation and IL-2 production in vitro. (A) Pl...
(A) Plates were coated with anti-CD3 at the indicated concentrations in the presence of 5 μg/ml VSIG4-Ig or control IgG1. Proliferation of purified CD4+ T cells was monitored after 2 days by [3H]thymidine incorporation. (B) Plates were coated with anti-CD3 at 0.5 μg/ml in the presence of 5 or 10 μg/ml VSIG4-Ig or IgG1 at the indicated concentrations. CD8+ T cell proliferation was monitored after 2 days by [3H]thymidine incorporation. (C) Costimulation assays were performed with purified CD4+ T cells with a fixed concentration of anti-CD3 (0.5 μg/ml) in the presence or absence of anti-CD28 (2 μg/ml) with either 5 μg/ml VSIG4-Ig or control IgG1. (D) IL-2 production of CD4+ T cells stimulated with 0.5 μg/ml anti-CD3 in the presence of 5 μg/ml VSIG4-Ig or control IgG1. (E) Proliferation assays were performed in the presence of 0.5 μg/ml anti-CD3 and VSIG4-Ig, PD-L1–Ig, PD-L2–Ig, or control IgG1 at a concentration of 10 μg/ml. (F) Proliferation assays were performed in the presence of 0.5 μg/ml anti-CD3 and VSIG4-Ig or control IgG1 at a concentration of 5 or 10 μg/ml in the absence or presence of 10 ng/ml IL-2. Error bars represent standard deviations for data from experiments performed in triplicate. Representative data from least 2 independent experiments are shown. The difference between VSIG4-Ig– and IgG1-treated cells was significant in all panels shown (P < 0.05). In F, the difference between VSIG4-Ig– and IgG1-treated cells in the presence of IL-2 was not significant (P > 0.05).