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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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Research Article Immunology Article has an altmetric score of 7

VSIG4, a B7 family–related protein, is a negative regulator of T cell activation

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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 2

VSIG4 is expressed on resting peritoneal macrophages and downregulated upon activation.

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VSIG4 is expressed on resting peritoneal macrophages and downregulated u...
(A) VSIG4 copies normalized to GAPDH in the respective tissues or cell types are shown. Sm muscle, smooth muscle. (B) Characterization of anti-VSIG4 rabbit serum. Left: EL4 (filled histogram) or EL4-VSIG4 cells (black lines) were stained with anti-VSIG4. Right: Western blot analysis of lysates from 293 and 293-VSIG4 cells with anti-VSIG4. (C) Peritoneal macrophages (Mϕ), monocytes, and neutrophils from blood and spleen and activated and naive DCs were stained with anti-VSIG4 (black lines) and preimmune serum (filled histograms). Gating markers are indicated above the histograms. Half of the CD11b+/Gr1– cells from the peritoneum (resident macrophages) showed VSIG4 expression. (D) Resting peritoneal macrophages and macrophages activated in vivo by thioglycolate (Thio) or LPS for 3 days were isolated, stained for the expression of VSIG4, and analyzed by FACS as described for C. Histograms of the gated CD11b+/Gr1– cell population are shown. (E) Resting peritoneal macrophages and macrophages activated in vivo by thioglycolate and PBMCs from the same animals were isolated and analyzed for VSIG4 expression by Western blotting using polyclonal anti-VSIG4 antibodies. PerC, peritoneal cells. (F) Dot plots of cells isolated from the peritoneum and stained with the indicated cell-surface marker and VSIG4 rabbit serum. (G) Freshly isolated peritoneal macrophages were either stained directly or cultivated in the presence or absence of 10 μg/ml LPS for 3 days and stained with anti-VSIG4 (black lines) or preimmune serum (filled histogram). Histograms of the gated CD11b+/Gr1low cell population are shown. Representative stainings of at least 2 independent experiments are shown.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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