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 7

Soluble VSIG4 inhibits induction of CTL responses and Th cell–dependent humoral immune responses in vivo.

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Soluble VSIG4 inhibits induction of CTL responses and Th cell–dependent ...
(A) Experimental diagram. Mice were injected with VSIG4-Ig or control IgG i.p. on days –1, 1, and 3 and immunized with Qβ-p33 VLPs with CpGs on day 0. Qβ-specific IgM and IgG responses were measured after 4 and 10 days. p33-specific CD8+ T cells were determined in the blood by tetramer staining on day 7. Mice were sacrificed on day 10, and levels of Qβ-specific B cells, AFCs, and p33-specific IFN-γ–expressing CD8+ T cells were determined from spleens. (B–G) Averages of 2 independent experiments ± SEM are shown (n = 8). Differences between VSIG4-Ig– and IgG1-treated mice were significant in B, C, and the right panel of D, as well as F and G. P values obtained by Student’s t test are shown. (B) Percentage p33-specific CD8+ T cells. (C) Percentage p33-specific CD8+ T cells after in vitro stimulation with p33-pulsed DCs 10 days after immunization. (D) ELISA titers of the Qβ-specific IgM and IgG responses. (E) Staining and gating strategy for the detection of isotype-switched B cells by FACS. Activated, isotype-switched B cells were found in the indicated gate. A representative example of Qβ-binding B cells in the indicated gate is shown in the right panel. (F) Percentage of Qβ-specific B cells within the indicated gate in E in mice 10 days after immunization. (G) Number of Qβ-specific AFCs per 106 splenocytes as determined by ELISPOT are shown.